PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34396568-0 2021 Melatonin and its derivative disrupt cancer stem-like phenotypes of lung cancer cells via AKT downregulation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 90-93 34953312-0 2022 Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 57-60 34953312-15 2022 PA decreased PI3K and Akt phosphorylation, whereas melatonin increased p-PI3K and p-Akt levels. Melatonin 51-60 AKT serine/threonine kinase 1 Homo sapiens 84-87 34953312-16 2022 Melatonin can reduce IR in GCs and PA-induced SVOG cells via the PI3K/Akt signaling pathway, providing more evidence for treating polycystic ovary syndrome. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 70-73 34079331-13 2021 Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3beta and beta-catenin pathways. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 94-97 34725795-11 2022 Expression of vascular endothelial VE-cadherin, ephrinA2 receptor (EPHA2), p-PI3K/phosphoinositide-3 kinase (PI3K) and phospho-AKT (p-AKT)/AKT ratios was decreased under the influence of Apatinib and a combination of Apatinib/melatonin (P <= 0.01). Melatonin 226-235 AKT serine/threonine kinase 1 Homo sapiens 127-130 34725795-11 2022 Expression of vascular endothelial VE-cadherin, ephrinA2 receptor (EPHA2), p-PI3K/phosphoinositide-3 kinase (PI3K) and phospho-AKT (p-AKT)/AKT ratios was decreased under the influence of Apatinib and a combination of Apatinib/melatonin (P <= 0.01). Melatonin 226-235 AKT serine/threonine kinase 1 Homo sapiens 134-137 34725795-11 2022 Expression of vascular endothelial VE-cadherin, ephrinA2 receptor (EPHA2), p-PI3K/phosphoinositide-3 kinase (PI3K) and phospho-AKT (p-AKT)/AKT ratios was decreased under the influence of Apatinib and a combination of Apatinib/melatonin (P <= 0.01). Melatonin 226-235 AKT serine/threonine kinase 1 Homo sapiens 139-142 34580235-0 2021 Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 121-124 34580235-8 2021 Melatonin was found to suppress the PI3K/Akt/mTOR signaling pathway in a time-dependent manner by inhibiting the phosphorylation of PI3K, Akt, and mTOR. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 41-44 34580235-8 2021 Melatonin was found to suppress the PI3K/Akt/mTOR signaling pathway in a time-dependent manner by inhibiting the phosphorylation of PI3K, Akt, and mTOR. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 138-141 34580235-11 2021 CONCLUSIONS: Our study revealed that melatonin could induce apoptosis by suppressing the PI3K/Akt/mTOR signaling pathway. Melatonin 37-46 AKT serine/threonine kinase 1 Homo sapiens 94-97 34165162-0 2021 Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR-223/PTEN/AKT signaling pathway. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 93-96 34758863-0 2021 Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 88-91 34660789-0 2021 Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 99-102 34660789-10 2021 Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. Melatonin 14-23 AKT serine/threonine kinase 1 Homo sapiens 142-145 34660789-11 2021 In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 114-117 35607451-0 2022 Melatonin increases growth properties in human dermal papilla spheroids by activating AKT/GSK3beta/beta-Catenin signaling pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 86-89 35607451-6 2022 The AKT/GSK3beta/beta-catenin signaling pathway associated with melatonin-induced beta-catenin stabilization in DP cells was investigated by analyzing changes in upstream regulator proteins, including AKT, GSK3beta, and their phosphorylated forms. Melatonin 64-73 AKT serine/threonine kinase 1 Homo sapiens 4-7 35607451-6 2022 The AKT/GSK3beta/beta-catenin signaling pathway associated with melatonin-induced beta-catenin stabilization in DP cells was investigated by analyzing changes in upstream regulator proteins, including AKT, GSK3beta, and their phosphorylated forms. Melatonin 64-73 AKT serine/threonine kinase 1 Homo sapiens 201-204 35607451-14 2022 Interestingly, melatonin induced the phosphorylation of protein kinase B/AKT at serine 473 residue and GSK-3beta at serine 9 residue. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 73-76 35625825-12 2022 Melatonin further enhanced the radiation-mediated inhibition of Akt. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 64-67 33065391-8 2020 Furthermore, the data demonstrated that melatonin could activate the PI3K/AKT signaling pathway, resulting in phosphorylation of GSK-3beta (Ser9) and upregulation of the Nrf2 protein in A549 cells, which ultimately attenuated LPS-induced EMT. Melatonin 40-49 AKT serine/threonine kinase 1 Homo sapiens 74-77 35607451-17 2022 Conclusion: Collectively, this report suggests that melatonin promotes growth properties by activating the AKT/GSK3beta/beta-catenin signaling pathway through melatonin receptors. Melatonin 52-61 AKT serine/threonine kinase 1 Homo sapiens 107-110 35607451-17 2022 Conclusion: Collectively, this report suggests that melatonin promotes growth properties by activating the AKT/GSK3beta/beta-catenin signaling pathway through melatonin receptors. Melatonin 159-168 AKT serine/threonine kinase 1 Homo sapiens 107-110 33226571-6 2021 Our results also showed that melatonin increased the activity of PI3K/AKT and DNA-PKcs knockdown in melatonin-treated HUVECs that lead to inactivation of PI3K/AKT signaling under oxidative stress with H2O2. Melatonin 29-38 AKT serine/threonine kinase 1 Homo sapiens 70-73 33226571-6 2021 Our results also showed that melatonin increased the activity of PI3K/AKT and DNA-PKcs knockdown in melatonin-treated HUVECs that lead to inactivation of PI3K/AKT signaling under oxidative stress with H2O2. Melatonin 29-38 AKT serine/threonine kinase 1 Homo sapiens 159-162 33226571-6 2021 Our results also showed that melatonin increased the activity of PI3K/AKT and DNA-PKcs knockdown in melatonin-treated HUVECs that lead to inactivation of PI3K/AKT signaling under oxidative stress with H2O2. Melatonin 100-109 AKT serine/threonine kinase 1 Homo sapiens 70-73 33226571-6 2021 Our results also showed that melatonin increased the activity of PI3K/AKT and DNA-PKcs knockdown in melatonin-treated HUVECs that lead to inactivation of PI3K/AKT signaling under oxidative stress with H2O2. Melatonin 100-109 AKT serine/threonine kinase 1 Homo sapiens 159-162 33226571-7 2021 Furthermore, blockade of PI3K/AKT signal with LY294002 significantly reduced melatonin-induced apoptosis inhibition in H2O2-treated HUVECs. Melatonin 77-86 AKT serine/threonine kinase 1 Homo sapiens 30-33 33226571-8 2021 Taken together, our findings identify a miR-101/DNA-PKcs/PI3K/AKT signaling pathway in melatonin-induced endothelial cell apoptosis inhibition under oxidative stress with H2O2. Melatonin 87-96 AKT serine/threonine kinase 1 Homo sapiens 62-65 33016468-7 2021 Additionally, SIRT6 shRNA or luzindole inhibited melatonin-induced AMPK-PGC-1alpha-AKT activation as well as its cardioprotective actions. Melatonin 49-58 AKT serine/threonine kinase 1 Homo sapiens 83-86 32791190-9 2020 Our results reveal that the MT2 receptor and activation of AKT are involved in melatonin-induced VEGF expression. Melatonin 79-88 AKT serine/threonine kinase 1 Homo sapiens 59-62 32962330-9 2020 Most of these downstream molecules, such as PI3K/AKT pathway components, also contribute to the cytoprotective effects of melatonin. Melatonin 122-131 AKT serine/threonine kinase 1 Homo sapiens 49-52 35625825-8 2022 Among them, melatonin elevated the levels of PTEN and NME1, and decreased the levels of SNAI2, ERBB2, AKT, SERPINE1, SFN, PLAU, ATM and N3RC1. Melatonin 12-21 AKT serine/threonine kinase 1 Homo sapiens 102-105 32758663-0 2020 Melatonin inhibits the apoptosis of rooster Leydig cells by suppressing oxidative stress via AKT-Nrf2 pathway activation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 93-96 32758663-9 2020 Furthermore, melatonin promoted the phosphorylation of AKT, while AKT inhibitor suppressed the Nrf2 pathway activated by melatonin and alleviated the inhibitory effects of melatonin on apoptosis and oxidative stress. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 55-58 32758663-9 2020 Furthermore, melatonin promoted the phosphorylation of AKT, while AKT inhibitor suppressed the Nrf2 pathway activated by melatonin and alleviated the inhibitory effects of melatonin on apoptosis and oxidative stress. Melatonin 121-130 AKT serine/threonine kinase 1 Homo sapiens 66-69 32758663-9 2020 Furthermore, melatonin promoted the phosphorylation of AKT, while AKT inhibitor suppressed the Nrf2 pathway activated by melatonin and alleviated the inhibitory effects of melatonin on apoptosis and oxidative stress. Melatonin 121-130 AKT serine/threonine kinase 1 Homo sapiens 66-69 32758663-10 2020 In conclusion, melatonin could inhibit apoptosis in rooster Leydig cells by suppressing oxidative stress via activation of the AKT-Nrf2 pathway. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 127-130 32935463-0 2020 Melatonin synergizes BRAF-targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 114-117 32935463-6 2020 Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Melatonin 53-62 AKT serine/threonine kinase 1 Homo sapiens 101-104 32792862-0 2020 Jagged2 progressively increased expression from Stage I to III of Bladder Cancer and Melatonin-mediated downregulation of Notch/Jagged2 suppresses the Bladder Tumorigenesis via inhibiting PI3K/AKT/mTOR/MMPs signaling. Melatonin 85-94 AKT serine/threonine kinase 1 Homo sapiens 193-196 33571963-6 2020 The increases in the phosphorylation of mammalian target of rapamycin (p-mTOR), raptor protein, and mTOR complex 1 (mTORC1) levels were consistent with the increments in the expressions of p-Akt (Ser473, Thr308) and stress-induced IRE1alpha/p-eIF2alpha proteins in the endoplasmic reticulum following melatonin treatment. Melatonin 301-310 AKT serine/threonine kinase 1 Homo sapiens 191-194 33571963-8 2020 These results indicate that nanomolar melatonin regulates insulin synthesis and secretion associated with membrane vesicle trafficking-related proteins, including Rab5, GOPC, p-Caveolin-1, EEA1, and clathrin, through the Akt/mTOR pathway. Melatonin 38-47 AKT serine/threonine kinase 1 Homo sapiens 221-224 32811805-8 2020 Moreover, we found that melatonin (MLT) effectively reduced the abdominal tumor burden of ovarian cancer induced by CRS, which was partially related to the inhibition of the NE/AKT/beta-catenin/SLUG axis. Melatonin 24-33 AKT serine/threonine kinase 1 Homo sapiens 177-180 32901009-0 2020 Correction: Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/beta-catenin/SLUG axis. Melatonin 12-21 AKT serine/threonine kinase 1 Homo sapiens 114-117 32649783-8 2020 In conclusion, melatonin improved sperm cryopreservation, perhaps by acting on MT1 via the PI3K-Akt-GSK 3beta pathway to inhibit mPTP opening. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 96-99 32863233-0 2020 Melatonin sensitises shikonin-induced cancer cell death mediated by oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 118-121 32863233-4 2020 We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Melatonin 39-42 AKT serine/threonine kinase 1 Homo sapiens 162-165 32792862-1 2020 Background: This study assessed the expression of Jagged2 in human bladder cancer (BC) tested the hypothesis that melatonin (Mel) inhibited the tumorigenesis of BC cells mainly through downregulating the Notch/Jagged2 and PI3K/AKT/mTOR/MMPs(2&9) signaling pathways. Melatonin 114-123 AKT serine/threonine kinase 1 Homo sapiens 227-230 32792862-1 2020 Background: This study assessed the expression of Jagged2 in human bladder cancer (BC) tested the hypothesis that melatonin (Mel) inhibited the tumorigenesis of BC cells mainly through downregulating the Notch/Jagged2 and PI3K/AKT/mTOR/MMPs(2&9) signaling pathways. Melatonin 125-128 AKT serine/threonine kinase 1 Homo sapiens 227-230 32598308-8 2020 Melatonin inhibited glucose-induced HUVEC apoptosis via PI3K/Akt signaling pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 61-64 32598308-11 2020 Conclusions In conclusion, our results suggested that melatonin exerted vasculoprotective effects against glucose-induced apoptosis in HUVEC through PI3K/Akt, Bcl-2 and oxLDL/LOX-1 signaling pathways. Melatonin 54-63 AKT serine/threonine kinase 1 Homo sapiens 154-157 32600435-0 2020 Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 148-151 32052470-0 2020 Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3-phosphoinositides. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 53-56 32547319-7 2020 Melatonin recovered the expression levels of PrPC under high glucose conditions via phosphorylation of Akt, resulting in the prevention of high glucose-induced fibrosis. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 103-106 32052470-5 2020 The underlying mechanism suggests that both extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Melatonin 176-178 AKT serine/threonine kinase 1 Homo sapiens 99-102 32052470-6 2020 Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3-kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Melatonin 270-272 AKT serine/threonine kinase 1 Homo sapiens 55-58 32052470-8 2020 In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1-orchestrated activation of ERK1/2 and Akt signaling. Melatonin 37-39 AKT serine/threonine kinase 1 Homo sapiens 148-151 32096202-14 2020 Melatonin exerted antiapoptotic effect on OGD/R treated SH SY5Y cells partly by activating Akt signaling. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 91-94 32179814-7 2020 Besides, melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1, ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. Melatonin 9-18 AKT serine/threonine kinase 1 Homo sapiens 163-167 32179814-7 2020 Besides, melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1, ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. Melatonin 9-18 AKT serine/threonine kinase 1 Homo sapiens 310-314 32096202-16 2020 CONCLUSIONS: Melatonin protected SH SY5Y cells from OGD/R induced oxidative stress, inflammation, apoptosis, and autophagy by blocking NF-kappaB signaling and activating Nrf2/HO-1, Akt, and mTOR/p70S6K/4E-BP-1 pathways, thereby indicating that melatonin is a potential and novel therapeutic drug for ischemic stroke. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 181-184 31836786-5 2019 By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3alphabeta, and p70S6K. Melatonin 103-112 AKT serine/threonine kinase 1 Homo sapiens 47-50 31605630-8 2020 Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin 41-50 AKT serine/threonine kinase 1 Homo sapiens 141-144 31836786-0 2019 Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 61-64 31836786-5 2019 By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3alphabeta, and p70S6K. Melatonin 103-112 AKT serine/threonine kinase 1 Homo sapiens 152-155 31836786-8 2019 Our data demonstrate that melatonin controls the expression of Bmal1 via PI3K/AKT signaling, and Bmal1 plays critical roles in cellular survival via activation of survival kinases. Melatonin 26-35 AKT serine/threonine kinase 1 Homo sapiens 78-81 31025320-7 2019 In addition, we found that melatonin-regulated Sirt3 expression in a manner dependent on the Akt pathway. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 93-96 31025320-0 2019 Melatonin attenuates TNF-alpha-mediated hepatocytes damage via inhibiting mitochondrial stress and activating the Akt-Sirt3 signaling pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 114-117 31619582-6 2019 Melatonin exposure activates the PI3K/AKT signaling pathway and its inhibition attenuates the stimulatory effect of melatonin on StAR expression. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 38-41 31619582-6 2019 Melatonin exposure activates the PI3K/AKT signaling pathway and its inhibition attenuates the stimulatory effect of melatonin on StAR expression. Melatonin 116-125 AKT serine/threonine kinase 1 Homo sapiens 38-41 31025320-8 2019 Blockade of the Akt pathway abolished the protective exerted by melatonin on mitochondria and hepatocyte under TNF-alpha treatment. Melatonin 64-73 AKT serine/threonine kinase 1 Homo sapiens 16-19 31025320-10 2019 However, melatonin significantly increases the activity of the Akt/Sirt3 axis and consequently maintains mitochondrial homeostasis, restoring hepatocyte viability in an inflammatory environment. Melatonin 9-18 AKT serine/threonine kinase 1 Homo sapiens 63-66 29322615-0 2018 Melatonin protects against Abeta-induced neurotoxicity in primary neurons via miR-132/PTEN/AKT/FOXO3a pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 91-94 30809951-8 2019 In AGS and MGC803 cells with melatonin exposure, cleaved Caspase 9 was upregulated and Caspase 3 was activated; moreover, MDM2 and AKT expression and phosphorylation were downregulated. Melatonin 29-38 AKT serine/threonine kinase 1 Homo sapiens 131-134 30809951-9 2019 Melatonin promoted apoptosis of AGS and MGC803 cells by the downregulation of AKT and MDM2. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 78-81 31354524-11 2019 Melatonin also counteracted the stimulatory effect of radiation on CXCL6, CCL2, ERK1, ERK2, and AKT1 mRNA expression and increased the inhibitory effect of radiation on NOS3 expression. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 96-100 31354524-13 2019 Melatonin potentiated the inhibitory effect on the activation of p-AKT and p-ERK exerted by radiation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 67-70 31354524-14 2019 Antiangiogenic effect of melatonin could be mediated through AKT and ERK pathways, proteins involved in vascular endothelial (VE) cell growth, cell proliferation, survival, migration, and angiogenesis. Melatonin 25-34 AKT serine/threonine kinase 1 Homo sapiens 61-64 30575440-6 2019 Melatonin can influence the two growth factor-induced phosphorylation of AKT (Ser473) but not ERK(1/2). Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 73-76 30575440-7 2019 Our results show that melatonin can inhibit growth factor-induced monolayer permeability of HUVECs by influencing the phosphorylation of AKT and VE-cadherin. Melatonin 22-31 AKT serine/threonine kinase 1 Homo sapiens 137-140 30648758-4 2019 We found that melatonin dose-dependently inhibits tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta expression through the PI3K/AKT, ERK, and NF-kappaB signaling pathways. Melatonin 14-23 AKT serine/threonine kinase 1 Homo sapiens 145-148 30648758-8 2019 Our results indicate that melatonin ameliorates RA by inhibiting TNF-alpha and IL-1beta production through downregulation of the PI3K/AKT, ERK, NF-kappaB signaling pathways, as well as miR-3150a-3p overexpression. Melatonin 26-35 AKT serine/threonine kinase 1 Homo sapiens 134-137 31024297-5 2019 Melatonin (5 mg/kg) attenuated ischemia-induced down regulation of NMDA receptor 2 (NR2a), postsynaptic density-95 (PSD95) and increases NR2a/PSD95 complex association, which further activates the pro-survival PI3K/Akt/GSK3beta pathway with mitigated collapsin response mediator protein 2 (CRMP2) phosphorylation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 215-218 30372570-0 2019 Melatonin-mediated downregulation of ZNF746 suppresses bladder tumorigenesis mainly through inhibiting the AKT-MMP-9 signaling pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 107-110 30372570-5 2019 Protein expression of ZNF746 in RT4/T24 cells and protein expression phosphorylated (p)-AKT/MMP-2/MMP-9 in HT1197/HT1376 cells were reduced following Mel treatment (all P < 0.001). Melatonin 150-153 AKT serine/threonine kinase 1 Homo sapiens 88-91 30372570-8 2019 In vivo study demonstrated that Mel treatment significantly suppressed cellular expressions of MMP-9/MMP-2, protein expressions of ZNF746/p-AKT, and tumor size (all P < 0.001). Melatonin 32-35 AKT serine/threonine kinase 1 Homo sapiens 140-143 30349079-0 2018 Melatonin suppresses TLR9-triggered proinflammatory cytokine production in macrophages by inhibiting ERK1/2 and AKT activation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 112-115 30349079-6 2018 Furthermore, melatonin did not affect mRNA expressions of TLR9 and MyD88 but attenuated TLR9 ligand-induced ERK1/2 and AKT phosphorylation without affecting p38 and NF-kappaB p65 phosphorylation. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 119-122 30349079-8 2018 Taken together, our results demonstrate that melatonin suppresses TLR9-triggered proinflammatory cytokines production in macrophages via melatonin membrane receptor-independent manners and probably through inhibiting ERK1/2 and AKT activation, which further elucidates the roles of melatonin in regulating TLR-mediated innate immune responses in macrophages. Melatonin 45-54 AKT serine/threonine kinase 1 Homo sapiens 228-231 31386965-7 2019 Melatonin-mediated inhibition of Ripk3 improved mitochondrial bioenergetics, reduced mitochondria-initiated oxidative damage, sustained mitochondrial dynamics, ameliorated ER stress, normalized calcium recycling, and activated cardioprotective signaling pathways (including AKT, ERK and AMPK) in cardiomyocytes. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 274-277 29322615-14 2018 Together, these results indicate that melatonin exerts its neuroprotective effect in Abeta-induced neurotoxicity via miR-132/PTEN/AKT/FOXO3a pathway. Melatonin 38-47 AKT serine/threonine kinase 1 Homo sapiens 130-133 29322615-13 2018 We also found that VO-OHpic (PTEN inhibitor) could counteract Abeta-induced neuronal damage, and LY294002 (AKT inhibitor) suppressed the protective effect of melatonin. Melatonin 158-167 AKT serine/threonine kinase 1 Homo sapiens 107-110 29783631-9 2018 Experiments performed to gain insights into the possible mechanism of action of the melatonin derivative revealed that UCM 1037 down-regulates androgen receptor levels and Akt activation in LNCaP and 22Rv1 cells. Melatonin 84-93 AKT serine/threonine kinase 1 Homo sapiens 172-175 28655071-7 2018 We found that by inducing phosphorylation of Akt and activating the Akt signaling pathway, melatonin enhanced catalase activity and thereby inhibited the accumulation of reactive oxygen species induced by p-cresol in mesenchymal stem cells, ultimately preventing abnormal activation of autophagy. Melatonin 91-100 AKT serine/threonine kinase 1 Homo sapiens 45-48 28655071-7 2018 We found that by inducing phosphorylation of Akt and activating the Akt signaling pathway, melatonin enhanced catalase activity and thereby inhibited the accumulation of reactive oxygen species induced by p-cresol in mesenchymal stem cells, ultimately preventing abnormal activation of autophagy. Melatonin 91-100 AKT serine/threonine kinase 1 Homo sapiens 68-71 29766567-6 2018 Moreover, melatonin increased and decreased the activation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2, respectively, in a dose-dependent manner in U2OS and HOS cells while exerting no evident influence on the level and activation of p38, Akt, FAK, steroid receptor coactivator, or Raf. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 284-287 29607540-5 2018 In HepG2 cells treated with 300 mumol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 mumol/L of melatonin. Melatonin 193-202 AKT serine/threonine kinase 1 Homo sapiens 73-76 29313427-0 2018 Melatonin therapy for blunt trauma and strenuous exercise: A mechanism involving cytokines, NFkappaB, Akt, MAFBX and MURF-1. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 102-105 29313427-8 2018 The general concept described in this review is that melatonin inhibits NFkappaB, reduces cytokine expression, increases Akt that downregulates the ratio of MAFBX and MURF-1 in order to limit the extent of muscle injury and promote muscle recovery post-injury. Melatonin 53-62 AKT serine/threonine kinase 1 Homo sapiens 121-124 29247557-0 2018 Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 88-91 29462594-9 2018 Our results further demonstrated that these promotional effects of melatonin were related with the activity of phosphorylation of AKT. Melatonin 67-76 AKT serine/threonine kinase 1 Homo sapiens 130-133 29462594-10 2018 Therefore, these outcomes propose that melatonin protects iPSC-derived NSCs from H2O2-induced injury through the mediation of melatonin receptor and PI3K/AKT signaling pathway. Melatonin 39-48 AKT serine/threonine kinase 1 Homo sapiens 154-157 29196809-0 2018 Melatonin affects membrane integrity, intracellular reactive oxygen species, caspase3 activity and AKT phosphorylation in frozen thawed human sperm. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 99-102 29196809-8 2018 The optimal melatonin concentration (3 mM) significantly decreased the intracellular reactive oxygen species levels, caspase-3 activity and the percentage of both dead and apoptotic-like sperm cells and increased the vitality, progressive motility and total motility and AKT phosphorylation compared with the control group. Melatonin 12-21 AKT serine/threonine kinase 1 Homo sapiens 271-274 29196809-9 2018 Thus, melatonin exerts protective effects against cryodamage during human spermatozoa cryopreservation and may exert its effects via the PI3K/AKT signaling pathway. Melatonin 6-15 AKT serine/threonine kinase 1 Homo sapiens 142-145 29247557-9 2018 Our results demonstrated that combined treatment with rapamycin and melatonin blocked the negative feedback loop from the specific downstream effector of mTOR activation S6K1 to Akt signalling, which decreased cell viability, proliferation and clonogenic capacity. Melatonin 68-77 AKT serine/threonine kinase 1 Homo sapiens 178-181 29484412-0 2018 Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 113-116 29484412-12 2018 Upstream regulators of the above proteins, MDM2, phospho-MDM2 (at Ser166) and AKT, phospho-AKT (at Thr308) were all attenuated by melatonin, which led to an increase in p53. Melatonin 130-139 AKT serine/threonine kinase 1 Homo sapiens 78-81 29484412-12 2018 Upstream regulators of the above proteins, MDM2, phospho-MDM2 (at Ser166) and AKT, phospho-AKT (at Thr308) were all attenuated by melatonin, which led to an increase in p53. Melatonin 130-139 AKT serine/threonine kinase 1 Homo sapiens 91-94 29484412-13 2018 The present study demonstrated that the oncostatic effects of melatonin on SGC-7901 GC cells are mediated via the blockade of the AKT/MDM2 intracellular pathway. Melatonin 62-71 AKT serine/threonine kinase 1 Homo sapiens 130-133 28719035-0 2017 Melatonin inhibits nucleus pulposus (NP) cell proliferation and extracellular matrix (ECM) remodeling via the melatonin membrane receptors mediated PI3K-Akt pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 153-156 29725496-3 2018 In this study, we found that melatonin impaired the proliferation and apoptosis resistance of oral cancer cells by inactivating ROS-dependent Akt signaling, involving in downregulation of cyclin D1, PCNA, and Bcl-2 and upregulation of Bax. Melatonin 29-38 AKT serine/threonine kinase 1 Homo sapiens 142-145 29725496-4 2018 Melatonin inhibited the migration and invasion of oral cancer cells by repressing ROS-activated Akt signaling, implicating with the reduction of Snail and Vimentin and the enhancement of E-cadherin. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 96-99 29725496-5 2018 Moreover, melatonin hampered vasculogenic mimicry of oral cancer cells through blockage of ROS-activated extracellular-regulated protein kinases (ERKs) and Akt pathways involving the hypoxia-inducible factor 1alpha. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 156-159 29725496-7 2018 Overall, these findings indicated that melatonin exerts antisurvival, antimotility, and antiangiogenesis effects on oral cancer partly by suppressing ROS-reliant Akt or ERK signaling. Melatonin 39-48 AKT serine/threonine kinase 1 Homo sapiens 162-165 29374563-7 2018 These effects are presumably governed by melatonin"s interventions in the main signal transduction pathways such as Akt and MAPK, independent of its antioxidant properties. Melatonin 41-50 AKT serine/threonine kinase 1 Homo sapiens 116-119 29330934-7 2018 Meanwhile, BPA-upregulated phosphorylation of ERK and AKT was decreased by melatonin treatment. Melatonin 75-84 AKT serine/threonine kinase 1 Homo sapiens 54-57 28912098-0 2017 Melatonin-mediated upregulation of Sirt3 attenuates sodium fluoride-induced hepatotoxicity by activating the MT1-PI3K/AKT-PGC-1alpha signaling pathway. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 118-121 28912098-8 2017 Analysis of the cell signaling pathway profiling systems and specific pathway inhibition indicated that melatonin enhances PGC-1alpha expression by activating the PI3K/AKT signaling pathway. Melatonin 104-113 AKT serine/threonine kinase 1 Homo sapiens 168-171 28912098-9 2017 Importantly, inhibition of melatonin receptor (MT)-1 blocked the melatonin-activated PI3K/AKT-PGC-1alpha-Sirt3 signaling. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 90-93 28580603-11 2017 In conclusion, we have demonstrated the melatonin stimulates PINK1 expression via an MT2 /Akt/NF-kappaB pathway, and such stimulation is important for the prevention of neuronal cell apoptosis under high glucose conditions. Melatonin 40-49 AKT serine/threonine kinase 1 Homo sapiens 90-93 28719035-7 2017 Signaling pathway analysis indicated that in the intervertebral disk tissues and NP cells, melatonin acted on MT1/2 and subsequently reduced phosphorylation of phosphoinositide 3-kinase p85 regulatory subunit, phosphoinositide-dependent kinase-1, and Akt. Melatonin 91-100 AKT serine/threonine kinase 1 Homo sapiens 251-254 26882203-9 2016 These findings demonstrate that melatonin attenuates cisplatin-induced follicle loss by preventing the phosphorylation of PTEN/AKT/FOXO3a pathway members; thus, melatonin is a potential therapeutic agent for ovarian protection and fertility preservation during chemotherapy in female cancer patients. Melatonin 32-41 AKT serine/threonine kinase 1 Homo sapiens 127-130 29207653-6 2017 Melatonin downregulated the HIF-1alpha protein synthesis through the inhibition of the mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase beta-1 (p70S6K)/ribosomal protein S6 (RP-S6) pathway, although the indole enhanced Akt phosphorylation by the mTORC1/C2 negative feedback. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 247-250 27130826-7 2016 The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. Melatonin 45-54 AKT serine/threonine kinase 1 Homo sapiens 19-22 27130826-7 2016 The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. Melatonin 99-108 AKT serine/threonine kinase 1 Homo sapiens 19-22 27130826-8 2016 These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 113-116 28580603-9 2017 We further showed melatonin stimulated Akt phosphorylation, which was followed by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) phosphorylation and nuclear translocation. Melatonin 18-27 AKT serine/threonine kinase 1 Homo sapiens 39-42 27121240-0 2016 Melatonin inhibits tumorigenicity of glioblastoma stem-like cells via the AKT-EZH2-STAT3 signaling axis. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 74-77 26732239-0 2016 Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPKs pathway and NF-kappaB DNA-binding activity. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 92-95 26732239-7 2016 Moreover, the Akt-mediated JNK1/2 and ERK1/2 signaling pathways were involved in melatonin-regulated MMP-9 transactivation and cell motility. Melatonin 81-90 AKT serine/threonine kinase 1 Homo sapiens 14-17 26882203-9 2016 These findings demonstrate that melatonin attenuates cisplatin-induced follicle loss by preventing the phosphorylation of PTEN/AKT/FOXO3a pathway members; thus, melatonin is a potential therapeutic agent for ovarian protection and fertility preservation during chemotherapy in female cancer patients. Melatonin 161-170 AKT serine/threonine kinase 1 Homo sapiens 127-130 26672764-0 2016 Melatonin inhibits AP-2beta/hTERT, NF-kappaB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 55-58 26877709-0 2016 Heat shock protein 27 downstream of P38-PI3K/Akt signaling antagonizes melatonin-induced apoptosis of SGC-7901 gastric cancer cells. Melatonin 71-80 AKT serine/threonine kinase 1 Homo sapiens 45-48 26877709-8 2016 Moreover, melatonin increased PI3K/Akt activation, LY294002 abrogated HSP27 activation and promoted cell apoptosis induced by melatonin. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 35-38 26877709-9 2016 Furthermore, melatonin increased P38 activity, and P38 inhibitor SB203580 inhibited melatonin-induced PI3K/Akt, HSP27 activation and accelerated cell apoptosis. Melatonin 84-93 AKT serine/threonine kinase 1 Homo sapiens 107-110 26877709-10 2016 CONCLUSION: In contrast to the well-established anti-cancer properties of melatonin, our study revealed clearly a distinguishable anti-apoptotic pathway induced by melatonin, that is, HSP27 plays a crucial role in apoptotic resistance in melatonin-treated gastric cancer cells, and its activation is most likely via the activation of P38/PI3K/Akt signaling. Melatonin 164-173 AKT serine/threonine kinase 1 Homo sapiens 343-346 26877709-10 2016 CONCLUSION: In contrast to the well-established anti-cancer properties of melatonin, our study revealed clearly a distinguishable anti-apoptotic pathway induced by melatonin, that is, HSP27 plays a crucial role in apoptotic resistance in melatonin-treated gastric cancer cells, and its activation is most likely via the activation of P38/PI3K/Akt signaling. Melatonin 164-173 AKT serine/threonine kinase 1 Homo sapiens 343-346 26672764-8 2016 Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 81-84 26672764-9 2016 Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2beta/hTERT, NF-kappaB/COX-2 and Akt/ERK signaling pathways. Melatonin 44-53 AKT serine/threonine kinase 1 Homo sapiens 179-182 27832629-2 2016 Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. Melatonin 111-120 AKT serine/threonine kinase 1 Homo sapiens 44-47 26607298-5 2016 Furthermore, melatonin completely suppressed the phospho-activation of ERK 1/2, AKT, GSK3beta and NF-kB (p65). Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 80-83 27832629-3 2016 AIMS: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin"s antiproliferative actions on the human MG-63 osteosarcoma cells. Melatonin 93-102 AKT serine/threonine kinase 1 Homo sapiens 54-57 25368672-0 2014 Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 40-43 26416428-9 2015 Levels of phosphorylated Akt, anti-apoptotic Bcl-xL, pro-apoptotic Bax and endothelial nitric oxide synthase (NOS) were re-regulated after combined oxygen and melatonin delivery, whereas neuronal and inducible NOS, which were increased by oxygen treatment, were not influenced by melatonin. Melatonin 159-168 AKT serine/threonine kinase 1 Homo sapiens 25-28 25857269-3 2015 Melatonin inhibits human breast cancer growth via mechanisms that include the suppression of tumor metabolism and inhibition of expression or phospho-activation of the receptor kinases AKT and ERK1/2 and various other kinases and transcription factors. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 185-188 25393881-5 2015 We show that the combination of melatonin with a fragment endowed with AChE inhibition in a unique chemical structure, ITH91/IQM157, can reduce neuronal cell death induced by Abeta and OA by a signaling pathway that implicates both nicotinic and melatonin receptors, PKC, Akt, ERK1/2, and induction of hemoxygenase-1. Melatonin 32-41 AKT serine/threonine kinase 1 Homo sapiens 272-275 25578604-5 2015 Melatonin treatment for 24-h decreased the levels of phospho-ERK1/2, but significantly increased Akt phosphorylation and protein expression of the histone acetyltransferase, p300. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 97-100 25578604-7 2015 Furthermore, upregulation of the histone acetyltransferase/transcriptional co-activator p300, along with phosphorylation of Akt, which is essential for p300 activation, appear to be key mechanisms underlying the epigenetic effects of melatonin. Melatonin 234-243 AKT serine/threonine kinase 1 Homo sapiens 124-127 25705693-9 2015 In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 78-81 24920214-10 2014 Herein, we demonstrated that melatonin drastically down-regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt-PI3K-dependent MDM2 phosphorylation. Melatonin 29-38 AKT serine/threonine kinase 1 Homo sapiens 181-184 24920214-10 2014 Herein, we demonstrated that melatonin drastically down-regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt-PI3K-dependent MDM2 phosphorylation. Melatonin 144-153 AKT serine/threonine kinase 1 Homo sapiens 181-184 23710615-10 2013 Furthermore, we found that melatonin is a potent activator of Akt in HLECs. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 62-65 24033914-6 2013 Melatonin inhibited Akt activation, thus decreasing P-GSK3B at serine 9 (i.e., increasing GSK3B activity) and subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by IL-17 alone or by a combination of insulin and IL-17. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 20-23 25199820-6 2014 Melatonin-mediated cell death resulted in decreased phosphorylation of EGFR and Akt, leading to attenuated expression of survival proteins, such as Bcl-2, Bcl-xL and survivin, and activated caspase 3 in H1975 cells, but not in HCC827 cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 80-83 23679681-8 2013 Melatonin also reduced the expression of COX-2 and inhibited AKT activation in HepG2 and SMMC-7721 cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 61-64 23679681-9 2013 Inhibition of COX-2 activity with the selective inhibitor, NS398, and inhibition of AKT activation using the PI3K inhibitor, LY294002, in tumor cells confirmed that melatonin-induced apoptosis was COX-2/PI3K/AKT-dependent, suggesting that the COX-2/PI3K/AKT pathway plays a role in melatonin inhibition of IAPs. Melatonin 165-174 AKT serine/threonine kinase 1 Homo sapiens 84-87 23679681-9 2013 Inhibition of COX-2 activity with the selective inhibitor, NS398, and inhibition of AKT activation using the PI3K inhibitor, LY294002, in tumor cells confirmed that melatonin-induced apoptosis was COX-2/PI3K/AKT-dependent, suggesting that the COX-2/PI3K/AKT pathway plays a role in melatonin inhibition of IAPs. Melatonin 165-174 AKT serine/threonine kinase 1 Homo sapiens 208-211 23679681-9 2013 Inhibition of COX-2 activity with the selective inhibitor, NS398, and inhibition of AKT activation using the PI3K inhibitor, LY294002, in tumor cells confirmed that melatonin-induced apoptosis was COX-2/PI3K/AKT-dependent, suggesting that the COX-2/PI3K/AKT pathway plays a role in melatonin inhibition of IAPs. Melatonin 165-174 AKT serine/threonine kinase 1 Homo sapiens 208-211 23679681-10 2013 Taken together, these results suggest that melatonin overcomes apoptosis resistance by the suppressing survivin and XIAP via the COX-2/PI3K/AKT pathway in HCC cells. Melatonin 43-52 AKT serine/threonine kinase 1 Homo sapiens 140-143 23711089-8 2013 Simultaneously, the expression of phosphorylated AKT (p-AKT) was elevated in HepG2 and SMMC-7721 cells given tunicamycin but reduced in the presence of melatonin. Melatonin 152-161 AKT serine/threonine kinase 1 Homo sapiens 49-52 23711089-8 2013 Simultaneously, the expression of phosphorylated AKT (p-AKT) was elevated in HepG2 and SMMC-7721 cells given tunicamycin but reduced in the presence of melatonin. Melatonin 152-161 AKT serine/threonine kinase 1 Homo sapiens 56-59 23711089-9 2013 Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. Melatonin 96-105 AKT serine/threonine kinase 1 Homo sapiens 43-46 23711089-9 2013 Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. Melatonin 96-105 AKT serine/threonine kinase 1 Homo sapiens 290-293 23711089-9 2013 Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. Melatonin 305-314 AKT serine/threonine kinase 1 Homo sapiens 43-46 23711089-10 2013 These results demonstrate that melatonin attenuates ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by down-regulating the PI3K/AKT pathway, increasing the levels of CHOP and decreasing the levels of Survivin. Melatonin 31-40 AKT serine/threonine kinase 1 Homo sapiens 164-167 23002080-4 2012 Melatonin activates GSK3beta by inhibiting the serine-threonine kinase Akt phosphorylation, inducing beta-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 71-74 22686283-7 2012 Administration of melatonin following trauma-hemorrhage normalized liver Akt phosphorylation (0.993 +- 0.061), further increased mammalian target of rapamycin (mTOR) activation (5.263 +- 0.338 versus 2.556 +- 0.225) and HO-1 expression (5.285 +- 0.325 versus 2.546 +- 0.262), and reduced cleaved caspase-3 levels (2.155 +- 0.297 versus 5.166 +- 0.309). Melatonin 18-27 AKT serine/threonine kinase 1 Homo sapiens 73-76 22335196-0 2012 Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells. Melatonin 69-78 AKT serine/threonine kinase 1 Homo sapiens 40-43 22507555-7 2012 Melatonin blocked H(2) O(2) -induced phosphorylation of PI3K/Akt, p38, ERK, JNK, and MAPK, as well as activation of NF-kappaB, which was reversed by sirtinol and SIRT1 siRNA. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 61-64 22335196-7 2012 Moreover, melatonin markedly inhibited phosphorylation of PI3K, Akt, PRAS40, and GSK-3 proteins, thereby inactivating the PI3K/Akt signaling pathway. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 64-67 22335196-7 2012 Moreover, melatonin markedly inhibited phosphorylation of PI3K, Akt, PRAS40, and GSK-3 proteins, thereby inactivating the PI3K/Akt signaling pathway. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 127-130 22335196-8 2012 Pretreatment with a PI3K- or an Akt-selective inhibitor or an Akt-specific siRNA blocked the melatonin-mediated inhibition of cell proliferation. Melatonin 93-102 AKT serine/threonine kinase 1 Homo sapiens 32-35 22335196-8 2012 Pretreatment with a PI3K- or an Akt-selective inhibitor or an Akt-specific siRNA blocked the melatonin-mediated inhibition of cell proliferation. Melatonin 93-102 AKT serine/threonine kinase 1 Homo sapiens 62-65 22335196-9 2012 Conversely, gene delivery of a constitutively active Akt effectively reversed the inhibition by melatonin. Melatonin 96-105 AKT serine/threonine kinase 1 Homo sapiens 53-56 22335196-12 2012 These results therefore indicate that melatonin inhibits cell proliferation and induces apoptosis in MDA-MB-361 breast cancer cells in vitro by simultaneously suppressing the COX-2/PGE2, p300/NF-kappaB, and PI3K/Akt/signaling and activating the Apaf-1/caspase-dependent apoptotic pathway. Melatonin 38-47 AKT serine/threonine kinase 1 Homo sapiens 212-215 22222116-6 2012 Moreover, melatonin inhibits the phosphorylation of the mammalian target of the rapamycin (mTOR) and Akt. Melatonin 10-19 AKT serine/threonine kinase 1 Homo sapiens 101-104 21988060-1 2012 Melatonin regulates mitogen-activated protein kinase (MAPK) and Akt signaling pathways. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 64-67 21988060-9 2012 These results suggest that the prevention of ERK activation is involved in melatonin-induced G(1) and G(2) /M phase arrest, and this inhibitory effect is potentially via the ERK, but not p38, JNK, or Akt, pathway. Melatonin 75-84 AKT serine/threonine kinase 1 Homo sapiens 201-204 21951103-8 2012 These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 133-136 21535449-0 2011 Melatonin inhibits IL-1beta-induced monolayer permeability of human umbilical vein endothelial cells via Rac activation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 105-108 23226532-8 2012 Furthermore, we found that melatonin is a potent activator of Akt in Muller cells. Melatonin 27-36 AKT serine/threonine kinase 1 Homo sapiens 62-65 19486272-5 2009 LMS perfused in situ for 150 min with arterial donor blood augmented with physiological nocturnal levels of melatonin showed a dose-dependent suppression of tumor cAMP production, LA uptake, 13-HODE release, extracellular signal-regulated kinase (ERK 1/2), mitogen activated protein kinase (MEK), Akt activation, and [(3)H]thymidine incorporation into DNA and DNA content. Melatonin 108-117 AKT serine/threonine kinase 1 Homo sapiens 297-300 21091766-0 2011 Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to TGFbeta-1-dependent growth inhibition of breast cancer cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 55-58 21091766-5 2011 Concomitantly, melatonin and D3, alone or in combination, caused a significant reduction in Akt phosphorylation and MDM2 values, with a consequent increase of p53/MDM2 ratio. Melatonin 15-24 AKT serine/threonine kinase 1 Homo sapiens 92-95 21091766-7 2011 Taken together, these results indicate that cytostatic effects triggered by melatonin and D3 are likely related to a complex TGFbeta-1-dependent mechanism, involving down-regulation of both MDM2 and Akt-phosphorylation. Melatonin 76-85 AKT serine/threonine kinase 1 Homo sapiens 199-202 21535449-7 2011 Furthermore, melatonin dramatically improved IL-1beta-induced Rac inactivation. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 62-65 21535449-8 2011 Our results show that the barrier-protective effects of melatonin on endothelial cells are mediated by Rac activation and leads to enhancement of adherens junctions. Melatonin 56-65 AKT serine/threonine kinase 1 Homo sapiens 103-106 21392092-5 2011 Furthermore, melatonin suppressed AKT/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway, which stabilizes HIF-1alpha via inhibition of von Hippel-Lindau tumor suppressor protein. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 34-37 19817973-0 2009 Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in hepatic cells. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 101-104 19817973-7 2009 In addition, melatonin increased the phosphorylation of subcellular signals at the level of protein kinase C zeta (PKCzeta), Akt, and glycogen synthase kinase 3beta (GSK3beta) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCzeta pseudo-peptide. Melatonin 13-22 AKT serine/threonine kinase 1 Homo sapiens 125-128 19196437-4 2009 In a thorough analysis by Western-blot of the potential pathways responsible for melatonin"s neuroprotective effects, we found an increase in the activation of prosurvival Akt. Melatonin 81-90 AKT serine/threonine kinase 1 Homo sapiens 172-175 19196437-9 2009 We conclude that the antiapoptotic effects of melatonin were mediated by two potential mechanisms: by increasing the activity of prosurvival pathways via Akt and by the prevention of DNA damage (via ATM inhibition) followed by the reduction of cell cycle re-entry. Melatonin 46-55 AKT serine/threonine kinase 1 Homo sapiens 154-157 19449447-8 2009 Melatonin frequently decreases cAMP, but also activates phospholipase C and protein kinase C, acts via the MAP kinase and PI3 kinase/Akt pathways, modulates large conductance Ca(2+)-activated K(+) and voltage-gated Ca(2+) channels. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 133-136 18721861-1 2008 We previously reported that melatonin prevents neuronal cell death in ischemic brain injury through the activation of Akt and the inhibition of apoptotic cell death. Melatonin 28-37 AKT serine/threonine kinase 1 Homo sapiens 118-121 18721861-8 2008 Melatonin prevented the injury-induced decrease in Akt activation and phosphorylation of mTOR and p70S6 kinases, and the subsequent decrease in S6 phosphorylation. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 51-54 18298462-6 2008 Melatonin inhibits the phosphorylation of the p47(phox) subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47(phox) and p67(phox) subunit to the membrane, down-regulates the binding of p47(phox) to gp91(phox), and impairs the assembly of NADPH oxidase. Melatonin 0-9 AKT serine/threonine kinase 1 Homo sapiens 92-95 18078454-6 2008 We also found that melatonin treatment induced the activation of Akt/PKB and the phosphorylation of GSK3alpha/beta and Bad. Melatonin 19-28 AKT serine/threonine kinase 1 Homo sapiens 65-72 18078456-10 2008 High concentrations of melatonin inhibited both NF-kappaB expression and its binding ability to DNA, possibly through inactivation of ERK/Akt /PKC pathways. Melatonin 23-32 AKT serine/threonine kinase 1 Homo sapiens 138-141 18078456-11 2008 Taken together, high concentrations of melatonin markedly reduced HUVEC proliferation; the antiproliferative action of melatonin was closely correlated with following pathway: melatonin receptors/ERK/PI3K/Akt/PKC/ NF-kappaB. Melatonin 39-48 AKT serine/threonine kinase 1 Homo sapiens 205-208 18078456-11 2008 Taken together, high concentrations of melatonin markedly reduced HUVEC proliferation; the antiproliferative action of melatonin was closely correlated with following pathway: melatonin receptors/ERK/PI3K/Akt/PKC/ NF-kappaB. Melatonin 119-128 AKT serine/threonine kinase 1 Homo sapiens 205-208 17803520-6 2007 Activation of PKC by incubation with triphorbol ester acetate (TPA) blocks the inhibitory effect of melatonin on Akt and NF-kappaB activity. Melatonin 100-109 AKT serine/threonine kinase 1 Homo sapiens 113-116 17803520-8 2007 Taken together, these results suggest that melatonin"s oncostatic effect on glioma cells is mediated, at least in part, by the inhibition of PKC activity which, in turn, results in Akt and NF-kappaB activity inhibition and modulation of cell cycle-related gene expression. Melatonin 43-52 AKT serine/threonine kinase 1 Homo sapiens 181-184