PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33177647-6 2020 The activation of p53 through the cooperative effects of these unidentified component(s), caffeine, and tamoxifen appeared to be due to the suppression of the ERK and Akt pathways. Caffeine 90-98 tumor protein p53 Homo sapiens 18-21 31168028-8 2019 The antioxidant N-acetylcysteine reduced the expression of phosphorylated ATM and H2AX, and the ATM inhibitor, caffeine, inhibited p53 activation. Caffeine 111-119 tumor protein p53 Homo sapiens 131-134 33015038-7 2020 Mechanistically, caffeine bound to SIRT3 with high affinity (K D = 6.858 x 10-7 M); the binding affinity between SIRT3 and its substrate acetylated p53 was also 9.03 (without NAD+) or 6.87 (with NAD+) times higher in the presence of caffeine. Caffeine 17-25 tumor protein p53 Homo sapiens 148-151 32062581-3 2020 Caffeine exposure also induced a strong DDR along with subsequent activation of wildtype p53 protein. Caffeine 0-8 tumor protein p53 Homo sapiens 89-92 32062581-10 2020 Thus, prolonged caffeine exposure stalls the cell cycle, induces a p53-mediated apoptotic response and a down-regulation of critical HR proteins, and for reasons discussed, stimulates early steps of HR, but not the formation of complete recombination products. Caffeine 16-24 tumor protein p53 Homo sapiens 67-70 25482947-6 2014 We found that inhibitors of the mTOR pathway including rapamycin, wortmannin, and caffeine blunted the p53 response to nucleolar stress induced by actinomycin D. Caffeine 82-90 tumor protein p53 Homo sapiens 103-106 30050935-7 2018 Mechanistic study showed that coadministration of caffeine and TMZ suppressed the phosphorylation of ATM and p53 and downregulated p21 expression, thus releasing DNA-damaged cells from G2 arrest into premature mitosis. Caffeine 50-58 tumor protein p53 Homo sapiens 109-112 30050935-10 2018 In conclusion, our study demonstrated that caffeine enhanced the efficacy of TMZ through mitotic cell death by impeding ATM/p53/p21-mediated G2 arrest. Caffeine 43-51 tumor protein p53 Homo sapiens 124-127 24444450-7 2014 The ACR-induced increases in the levels of p53 and pp53 in primary astrocytes could be attenuated by caffeine. Caffeine 101-109 tumor protein p53 Homo sapiens 43-46 24595168-4 2014 METHODOLOGY/PRINCIPAL FINDINGS: We have shown here that caffeine up-regulates the tumor suppressor proteins p16, p21, p53 and Cav-1, and reduces the expression/secretion of various cytokines (IL-6, TGF-beta, SDF-1 and MMP-2), and down-regulates alpha-SMA. Caffeine 56-64 tumor protein p53 Homo sapiens 118-121 30197757-8 2018 Cross-talk between Zac1, IL-11, p53, and suppressor of cytokine signaling 3 was differentially affected by copper sulfate, digoxin, and caffeine. Caffeine 136-144 tumor protein p53 Homo sapiens 32-35 26965143-5 2016 Specifically, either inhibition of ATM with caffeine or mutation of p53 (serine 15 to alanine) restored MDM2-dependent polyubiquitination of otherwise monoubiquitinated mutant p53. Caffeine 44-52 tumor protein p53 Homo sapiens 176-179 26965143-6 2016 Caffeine treatment rescued MDM2-dependent proteasome degradation of mutant p53 in cells exhibiting active DNA damage signaling, and ATM knockdown phenocopied the caffeine effect. Caffeine 0-8 tumor protein p53 Homo sapiens 75-78 26521794-0 2015 Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis. Caffeine 0-8 tumor protein p53 Homo sapiens 141-144 26521794-11 2015 RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. Caffeine 17-25 tumor protein p53 Homo sapiens 61-64 26521794-11 2015 RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. Caffeine 17-25 tumor protein p53 Homo sapiens 69-72 26521794-13 2015 CONCLUSION: Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis. Caffeine 12-20 tumor protein p53 Homo sapiens 124-127 24333670-2 2014 The detailed mechanisms of caffeine in tumor suppression via tumor suppressor protein p53 remain unclear. Caffeine 27-35 tumor protein p53 Homo sapiens 86-89 24333670-4 2014 In this study, we investigated how caffeine modulated cell cycle arrest and apoptosis via the expression of various alternatively spliced p53 isoforms. Caffeine 35-43 tumor protein p53 Homo sapiens 138-141 24333670-5 2014 Caffeine reduced p53alpha expression and induced the expression of p53beta, which contains an alternatively spliced p53 C-terminus. Caffeine 0-8 tumor protein p53 Homo sapiens 17-20 24333670-5 2014 Caffeine reduced p53alpha expression and induced the expression of p53beta, which contains an alternatively spliced p53 C-terminus. Caffeine 0-8 tumor protein p53 Homo sapiens 67-70 24333670-7 2014 Serine/arginine-rich splicing factor 3 was a promising candidate for the serine/arginine-rich splicing factors responsible for the alternative splicing of p53 in response to caffeine treatment. Caffeine 174-182 tumor protein p53 Homo sapiens 155-158 24333670-8 2014 In addition to p53-dependent functions, multiple target genes of serine/arginine-rich splicing factor 3 suggest that caffeine can regulate epithelial-mesenchymal-transition and hypoxic conditions to inhibit the survival of tumor cells. Caffeine 117-125 tumor protein p53 Homo sapiens 15-18 19536869-6 2009 The specific ATM inhibitor caffeine significantly decreased ISL-mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. Caffeine 27-35 tumor protein p53 Homo sapiens 122-125 22993301-2 2012 Caffeine affects tumour cells through various pathways, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3 and p53, and has therefore been indicated as being useful for the treatment of malignant tumours. Caffeine 0-8 tumor protein p53 Homo sapiens 183-186 21964066-6 2012 The pharmacologic inhibitor (caffeine) of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) protein kinases abolished activation of the p53-p21(WAF1) pathway upon FOXF1 knockdown, suggesting that suppression of FOXF1 function triggered the ATM/ATR-mediated DNA damage response. Caffeine 29-37 tumor protein p53 Homo sapiens 171-174 19735649-7 2009 Release of G2/M arrest by caffeine was accompanied by a decrease in the levels of p53/p21; however, gamma-H2AX levels were unchanged. Caffeine 26-34 tumor protein p53 Homo sapiens 82-85 19705844-6 2009 The specific ATM inhibitor caffeine significantly decreased tricetin-mediated G2/M arrest by inhibiting the phosphorylation of p53 (serine 15) and Chk2. Caffeine 27-35 tumor protein p53 Homo sapiens 127-130 21081844-2 2011 All known mechanisms of apoptosis induced by caffeine act through cell cycle modulation or p53 induction. Caffeine 45-53 tumor protein p53 Homo sapiens 91-94 20413215-3 2010 However, GA-induced p53 activation could be partially reversed by caffeine, a PI3k inhibitor. Caffeine 66-74 tumor protein p53 Homo sapiens 20-23 20103602-9 2010 The p53 independency was also confirmed by a significant caffeine-mediated radiosensitization of the glioma cell lines T98G and U373MG that are deficient for both PTEN and p53. Caffeine 57-65 tumor protein p53 Homo sapiens 4-7 20103602-9 2010 The p53 independency was also confirmed by a significant caffeine-mediated radiosensitization of the glioma cell lines T98G and U373MG that are deficient for both PTEN and p53. Caffeine 57-65 tumor protein p53 Homo sapiens 172-175 18223691-9 2008 Inhibition of p53 transactivation by pifithrin-alpha or the kinase activity of ATM by either the specific ATM inhibitor KU-5593 or caffeine abrogated p21(WAF1/CIP1) upregulation, indicating that DAC upregulation of p21(WAF1/CIP1) was p53- and ATM-dependent in leukemia cells. Caffeine 131-139 tumor protein p53 Homo sapiens 14-17 18511169-6 2008 Specific ATM inhibitor, caffeine, significantly decreased KTA-mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. Caffeine 24-32 tumor protein p53 Homo sapiens 120-123 18223691-9 2008 Inhibition of p53 transactivation by pifithrin-alpha or the kinase activity of ATM by either the specific ATM inhibitor KU-5593 or caffeine abrogated p21(WAF1/CIP1) upregulation, indicating that DAC upregulation of p21(WAF1/CIP1) was p53- and ATM-dependent in leukemia cells. Caffeine 131-139 tumor protein p53 Homo sapiens 234-237 18440285-5 2008 Caffeine increased apoptosis levels and inhibited p53 activation in proliferating cells, suggesting a protective role for p53. Caffeine 0-8 tumor protein p53 Homo sapiens 50-53 18440285-5 2008 Caffeine increased apoptosis levels and inhibited p53 activation in proliferating cells, suggesting a protective role for p53. Caffeine 0-8 tumor protein p53 Homo sapiens 122-125 17510082-8 2007 Aspirin induced the phosphorylation of p53 at residue Ser15 within 8 h in a caffeine-dependent manner, and also caused the activation of checkpoint kinase 2 and the cleavage of caspase 7. Caffeine 76-84 tumor protein p53 Homo sapiens 39-42 18088187-5 2007 The G2 arrest in p53+/+ cells was abrogated by caffeine, but not by staurosporine and UCN-01, whereas the G2 arrest in p53-/- cells was sensitive to all three inhibitors. Caffeine 47-55 tumor protein p53 Homo sapiens 17-20 17638302-0 2007 Neuroprotective effects of caffeine against complex I inhibition-induced apoptosis are mediated by inhibition of the Atm/p53/E2F-1 path in cerebellar granule neurons. Caffeine 27-35 tumor protein p53 Homo sapiens 121-124 17638302-4 2007 Our data indicate that the neuroprotective effects of caffeine in the MPP+ model of apoptosis are mediated through activation of the ATM/p53 pathway. Caffeine 54-62 tumor protein p53 Homo sapiens 137-140 18507003-8 2008 CONCLUSION: These findings provide new insights into the molecular mechanisms of the synergistic effect of caffeine related to p53 gene status in osteosarcoma, providing candidates for an assay of responsiveness to caffeine-potentiated chemotherapy for osteosarcoma. Caffeine 107-115 tumor protein p53 Homo sapiens 127-130 18088187-8 2007 In the presence of caffeine Chk1 phosphorylation was inhibited regardless of p53 status. Caffeine 19-27 tumor protein p53 Homo sapiens 77-80 17727682-8 2007 Caffeine, an inhibitor of ataxia-telangiectasia mutated protein kinase, alleviated the genistein-induced p53 and CHK2 phosphorylation, suggesting the involvement of DNA damage at 30 microM. Caffeine 0-8 tumor protein p53 Homo sapiens 105-108 14751246-1 2004 Caffeine has been widely described as a chemo/radiosensitizing agent, presumably by inhibiting DNA repair, and affecting preferentially cells with an altered p53 status. Caffeine 0-8 tumor protein p53 Homo sapiens 158-161 17704360-9 2007 TP53-mutated glioma cell lines demonstrated a very prominent dose-responsive G2 checkpoint and were sensitized to radiation by caffeine, which inhibits G2/S phase checkpoint activation. Caffeine 127-135 tumor protein p53 Homo sapiens 0-4 17096346-5 2007 The BITC-induced p53 phosphorylation was counteracted by caffeine treatment, implying the involvement of an ATM/ataxia telangiectasia and Rad3-related kinase signaling pathway. Caffeine 57-65 tumor protein p53 Homo sapiens 17-20 16489026-7 2006 Moreover, p53 was still stabilized in ataxia telangiectasia cells or in cells treated with caffeine, suggesting that ATM was not a critical determinant. Caffeine 91-99 tumor protein p53 Homo sapiens 10-13 16397265-3 2006 Based on clonogenic survival, the three single agents (IR, IUdR, and caffeine) as well as IUdR or caffeine combined with IR are less or equally effective in p53-deficient human tumor cells compared with p53-proficient tumor cells. Caffeine 69-77 tumor protein p53 Homo sapiens 157-160 16397265-3 2006 Based on clonogenic survival, the three single agents (IR, IUdR, and caffeine) as well as IUdR or caffeine combined with IR are less or equally effective in p53-deficient human tumor cells compared with p53-proficient tumor cells. Caffeine 98-106 tumor protein p53 Homo sapiens 157-160 16397265-9 2006 Cell cycle analyses also showed a greater abrogation of IR-induced S- and G2-phase arrests by caffeine in p53-deficient cells, particularly when combined with IUdR. Caffeine 94-102 tumor protein p53 Homo sapiens 106-109 16397265-11 2006 This differential dual mode of radiosensitization by combining IUdR and caffeine-like drugs (e.g., UCN-01) in p53-deficient human tumors may lead to a greater therapeutic gain. Caffeine 72-80 tumor protein p53 Homo sapiens 110-113 16024610-8 2005 NO treatment also induced the phosphorylation of p53 at Ser15; pretreatment with phosphoinositide-3 kinase (PI3K) family inhibitors, wortmannin, LY294002, and caffeine, blocked such phosphorylation, but the p38 mitogen-activated protein kinase inhibitor, SB203580, did not. Caffeine 159-167 tumor protein p53 Homo sapiens 49-52 15650224-4 2005 HHV-6B infection induced Ser20 and Ser15 phosphorylation on p53, and the latter was inhibited by caffeine, an ataxia telangiectasia mutated kinase inhibitor. Caffeine 97-105 tumor protein p53 Homo sapiens 60-63 15466201-5 2004 Sensitization to IR-induced apoptosis by caffeine or UCN-01 was abrogated neither by cycloheximide nor by pifithrin-alpha, an inhibitor of the transcriptional activity of p53. Caffeine 41-49 tumor protein p53 Homo sapiens 171-174 15169897-4 2004 The increase in p53 expression and the G(1) phase arrest could be blocked by caffeine, an inhibitor of ATR. Caffeine 77-85 tumor protein p53 Homo sapiens 16-19 17292432-6 2007 On the other hand, treatment with wortmannin or caffeine, the inhibitors to phosphatidylinositol 3-kinase related kinases (PIKKs), suppressed both NaVO(3)-induced Ser15 phosphorylation and accumulation of p53 protein. Caffeine 48-56 tumor protein p53 Homo sapiens 205-208 14643431-4 2003 Incubation in caffeine did not increase the percentage of cells entering the S phase 6-8h after irradiation; ATM-dependent phosphorylation of p53 and transactivation of p21(Cip1/Waf1) post-IR were resistant to caffeine. Caffeine 14-22 tumor protein p53 Homo sapiens 142-145 14757171-7 2004 Caffeine, an ATM kinase inhibitor, inhibited these effects of genistein on Chk2, p53, and p21waf1/cip1. Caffeine 0-8 tumor protein p53 Homo sapiens 81-84 14743382-6 2004 When their DNA is damaged, p53-defective tumor cells preferentially arrest in S or G2 phase where they are susceptible to checkpoint inhibitors such as caffeine and UCN-01. Caffeine 152-160 tumor protein p53 Homo sapiens 27-30 12902982-6 2003 Treatment with the ATM/ATR kinase inhibitor caffeine prevented p53 accumulation upon activation of Myc or E2F1. Caffeine 44-52 tumor protein p53 Homo sapiens 63-66 14599774-3 2003 Pentoxifylline and the related drug Caffeine are known radiosensitizers especially in p53 mutant cells. Caffeine 36-44 tumor protein p53 Homo sapiens 86-89 12907610-11 2003 These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase 3 pathways. Caffeine 44-52 tumor protein p53 Homo sapiens 64-67 12874009-3 2003 In HT1080 cells expressing a dominant-negative form of p53, treatment with etoposide still caused G(2) arrest, but the arrest could be overcome by additional treatment with caffeine, which inhibits the damage-responsive kinases ataxia telangiectasia mutated (ATM) and atm and rad3-related (ATR). Caffeine 173-181 tumor protein p53 Homo sapiens 55-58 12811820-0 2003 Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in NB4 promyelocytic leukemia cells. Caffeine 0-8 tumor protein p53 Homo sapiens 55-58 12811820-1 2003 Methylxantine derivative, caffeine, is known to prevent the p53-dependent apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase, which activates p53 by phosphorylation of the Ser-15 residue. Caffeine 26-34 tumor protein p53 Homo sapiens 60-63 12811820-1 2003 Methylxantine derivative, caffeine, is known to prevent the p53-dependent apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase, which activates p53 by phosphorylation of the Ser-15 residue. Caffeine 26-34 tumor protein p53 Homo sapiens 170-173 12811820-2 2003 In contrast, it has been reported that caffeine induces p53-mediated apoptosis through Bax protein in non-small-cell lung cancer cells. Caffeine 39-47 tumor protein p53 Homo sapiens 56-59 12811820-6 2003 Caffeine induced G(2)/M phase cell cycle arrest in NB4 cells in association with the induction of phosphorylation at the Ser-15 residue of p53 and induction of tyrosine phosphorylation of cdc2. Caffeine 0-8 tumor protein p53 Homo sapiens 139-142 12811820-8 2003 Interestingly, the antisense oligonucleotides for p53 significantly reduced p53 expression and caffeine-induced G(2)/M phase cell cycle arrest in NB4 cells. Caffeine 95-103 tumor protein p53 Homo sapiens 50-53 12811820-9 2003 These results suggest that caffeine induces cell cycle arrest and apoptosis in association with activation of p53 by a novel pathway to phosphorylate the Ser-15 residue and induction of phosphorylation of cdc 2 in leukemic cells with normal p53. Caffeine 27-35 tumor protein p53 Homo sapiens 110-113 12811820-9 2003 These results suggest that caffeine induces cell cycle arrest and apoptosis in association with activation of p53 by a novel pathway to phosphorylate the Ser-15 residue and induction of phosphorylation of cdc 2 in leukemic cells with normal p53. Caffeine 27-35 tumor protein p53 Homo sapiens 241-244 12894503-3 2003 Caffeine, a nonspecific inhibitor of ATR, enhanced the cytotoxic effect of cisplatin, modestly decreased the p53 and p21WAF-1 response to cisplatin, and affected the cdc2-p34/cyclin B1 complex by decreasing both cyclin B1 protein accumulation and cdc2-p34 tyrosine 15 phosphorylation. Caffeine 0-8 tumor protein p53 Homo sapiens 109-112 12807744-3 2003 Interestingly, the methylxanthine caffeine can abrogate the p53 accumulation induced by certain DNA-damaging agents by an unknown mechanism. Caffeine 34-42 tumor protein p53 Homo sapiens 60-63 12807744-5 2003 Caffeine inhibited the accumulation of p53 induced by leptomycin B (LMB), an inhibitor of CRM1, but not N-acetyl-leu-leu-norleucinal, a proteasome inhibitor. Caffeine 0-8 tumor protein p53 Homo sapiens 39-42 12807744-6 2003 Furthermore, caffeine also inhibited the accumulation of p53 by a variety of stress-inducing agents in vivo, such as 5-fluorouracil, doxorubicin, mitomycin C, camptothecin and roscovitine. Caffeine 13-21 tumor protein p53 Homo sapiens 57-60 11835680-0 2002 Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner. Caffeine 0-8 tumor protein p53 Homo sapiens 17-21 12646262-4 2003 Administration of caffeine to G2-arrested cells induced a drastic change in cell phenotype, the nature of which depended on the status of p53. Caffeine 18-26 tumor protein p53 Homo sapiens 138-141 12646262-5 2003 Flow cytometric and microscopic observations revealed that cells that either contained or lacked p53 resumed their cell cycles and entered mitosis upon caffeine treatment. Caffeine 152-160 tumor protein p53 Homo sapiens 97-100 12719724-6 2003 An ATR-kinase dead mutant or caffeine, which blocks the kinase activity of ATR, effectively abolishes the ability of NO to cause p53 nuclear retention, concomitant with its inhibition of p53 serine 15 phosphorylation. Caffeine 29-37 tumor protein p53 Homo sapiens 129-132 12719724-6 2003 An ATR-kinase dead mutant or caffeine, which blocks the kinase activity of ATR, effectively abolishes the ability of NO to cause p53 nuclear retention, concomitant with its inhibition of p53 serine 15 phosphorylation. Caffeine 29-37 tumor protein p53 Homo sapiens 187-190 11835680-3 2002 Surprisingly, at a concentration of 5 mM, caffeine not only induced apoptosis by itself and acted synergistically to enhance radiation-induced apoptosis, but also induced a TP53-independent G(1)-phase arrest. Caffeine 42-50 tumor protein p53 Homo sapiens 173-177 12509296-10 2002 Since HPV16 (E6/E7) transformed XPV cells were highly UV sensitive and not further sensitized by caffeine, it appears likely that caffeine sensitization proceeds through a p53 pathway. Caffeine 130-138 tumor protein p53 Homo sapiens 172-175 11489880-0 2001 Caffeine sensitizes human H358 cell line to p53-mediated apoptosis by inducing mitochondrial translocation and conformational change of BAX protein. Caffeine 0-8 tumor protein p53 Homo sapiens 44-47 11745415-2 2001 This process was supposed to involve the tumor suppressor gene p53 as it was described that p53 negative cells were more sensitive to checkpoint inhibition by caffeine than the wildtype phenotype. Caffeine 159-167 tumor protein p53 Homo sapiens 63-66 11745415-2 2001 This process was supposed to involve the tumor suppressor gene p53 as it was described that p53 negative cells were more sensitive to checkpoint inhibition by caffeine than the wildtype phenotype. Caffeine 159-167 tumor protein p53 Homo sapiens 92-95 11745415-11 2001 In addition, caffeine restored a G1 delay after irradiation in the cell lines with abrogated p53 functions. Caffeine 13-21 tumor protein p53 Homo sapiens 93-96 11489880-8 2001 All together, caffeine synergizes with p53 for inducing cell death through a cell cycle-independent mechanism, involving mitochondrial translocation and conformational change of BAX protein. Caffeine 14-22 tumor protein p53 Homo sapiens 39-42 11677656-8 2001 Interestingly, caffeine and other methyl xanthines preferentially radiosensitize cells that lack normal p53 function. Caffeine 15-23 tumor protein p53 Homo sapiens 104-107 11291094-10 2001 Results of Western hybridization reveal a p53-independent mechanism of radiosensitization caused by caffeine. Caffeine 100-108 tumor protein p53 Homo sapiens 42-45 11447225-3 2001 Induction of phosphorylation of p53 on multiple serine residues by H(2)O(2) was caffeine-sensitive and blocked in ATM(-/-) cells. Caffeine 80-88 tumor protein p53 Homo sapiens 32-35 11302731-5 2001 On the other hand, treatment with wortmannin or caffeine suppressed CdCl(2)-induced Ser 15 phosphorylation and accumulation of p53 protein. Caffeine 48-56 tumor protein p53 Homo sapiens 127-130 10809772-6 2000 In contrast, caffeine abolishes the accumulation of p53 caused by all the compounds. Caffeine 13-21 tumor protein p53 Homo sapiens 52-55 10738085-3 2000 RESULTS: The radiosensitizing effect of caffeine (2 mM) expressed itself as a significant decrease in surviving fraction at 2 Gy and a significant increase in alpha-values in RT112 and TE671, both with non-functional p53. Caffeine 40-48 tumor protein p53 Homo sapiens 217-220 10762633-1 2000 Caffeine inhibits the G2 checkpoint activated by DNA damage and enhances the toxicity of DNA-damaging agents towards p53-defective cancer cells. Caffeine 0-8 tumor protein p53 Homo sapiens 117-120 10738085-9 2000 CONCLUSION: The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. Caffeine 107-115 tumor protein p53 Homo sapiens 44-47 10769661-1 2000 The present study was performed to investigate whether the introduction of a wild-type p53 gene into human osteosarcoma cells could alter the growth rate and enhance the cytocidal effect of cisplatin (CDDP) and the synergistic antitumor effect of caffeine. Caffeine 247-255 tumor protein p53 Homo sapiens 87-90 10769661-5 2000 Caffeine significantly potentiated the cytocidal effect of CDDP in the Saos2/p53 cells. Caffeine 0-8 tumor protein p53 Homo sapiens 77-80 10769661-6 2000 Furthermore, the TUNEL assay revealed that following treatment both with CDDP alone and with CDDP combined with caffeine, a higher percentage of the Saos2/p53 cells underwent apoptosis than did the parental Saos2 cells. Caffeine 112-120 tumor protein p53 Homo sapiens 155-158 10769661-7 2000 Therefore the cytocidal effect of CDDP and the synergistic antitumor effect of caffeine are enhanced by the introduction of a wild-type p53 gene into a human osteosarcoma cell line null for p53. Caffeine 79-87 tumor protein p53 Homo sapiens 136-139 10049063-0 1999 DNA damage-associated cell cycle and cell death control is differentially modulated by caffeine in clones with p53 mutations. Caffeine 87-95 tumor protein p53 Homo sapiens 111-114 10485486-6 1999 Similar concentrations of caffeine also inhibit gamma- and UV radiation-induced phosphorylation of p53 on Ser15, a modification that may be directly mediated by the ATM and ATR kinases. Caffeine 26-34 tumor protein p53 Homo sapiens 99-102 10571245-2 1999 Caffeine has been shown to abrogate the S and G2 arrest in p53-defective cells and to enhance cytotoxicity, but at concentrations too toxic to administer to humans. Caffeine 0-8 tumor protein p53 Homo sapiens 59-62 10331854-4 1999 RESULTS: Both BL-13 and BL-28 cells (each expressing p53 with a wild-type sequence) fail to arrest at the G2 checkpoint after radiation, but nevertheless caffeine did induce radiosensitization. Caffeine 154-162 tumor protein p53 Homo sapiens 53-56 10331854-5 1999 In contrast, in BL-17/2 cells (expressing p53 with a point mutation in codon 280), caffeine treatment abrogated the radiation-induced G2 arrest but was not accompanied by radiosensitization. Caffeine 83-91 tumor protein p53 Homo sapiens 42-45 10049063-1 1999 Caffeine is known to potentiate the cytotoxic effects of DNA damaging agents and increases the sensitivity of p53-deficient cells to X-irradiation (X-IR). Caffeine 0-8 tumor protein p53 Homo sapiens 110-113 10049063-7 1999 These results suggest that the cytocidal effect of caffeine may need to be verified independently of its cell cycle regulatory activities at least in some cases with p53 mutation. Caffeine 51-59 tumor protein p53 Homo sapiens 166-169 9393772-0 1997 Correspondence re: J. S. DeFrank et al., p53-null cells are more sensitive to ultraviolet light only in the presence of caffeine. Caffeine 120-128 tumor protein p53 Homo sapiens 41-44 9815821-8 1997 This suggests that radiosensitization by CAF and increased cell death is dependent on loss of wt p53 function. Caffeine 41-44 tumor protein p53 Homo sapiens 97-100 9815821-10 1997 These results demonstrate that G2 checkpoint inhibition with CAF leads to preferential IR cell killing in cell lines in which wt p53 is inactivated and that this increased cell killing is not necessarily dependent on increased IR-induced apoptosis. Caffeine 61-64 tumor protein p53 Homo sapiens 129-132 9815821-6 1997 This p53-defective cell line was also radiosensitized by CAF, whereas the vector control (AA/PCMV/D), which retained wt p53 activity, was not. Caffeine 57-60 tumor protein p53 Homo sapiens 5-8 8837615-0 1996 Selective radiosensitization of p53-deficient cells by caffeine-mediated activation of p34cdc2 kinase. Caffeine 55-63 tumor protein p53 Homo sapiens 32-35 8968086-0 1996 p53-null cells are more sensitive to ultraviolet light only in the presence of caffeine. Caffeine 79-87 tumor protein p53 Homo sapiens 0-3 8968086-1 1996 We have shown previously that p53(-/-) fibroblasts show greater sensitization by caffeine to the lethal effects of ionizing radiation compared with p53(+/+) cells. Caffeine 81-89 tumor protein p53 Homo sapiens 30-33 8968086-4 1996 However, the introduction of 2 mM caffeine led to a sensitization enhancement ratio (at 10% survival) of 1.8 in p53(-/-) cells, but only 1.3 in wild-type (p53+/+) cells. Caffeine 34-42 tumor protein p53 Homo sapiens 112-115 8968086-4 1996 However, the introduction of 2 mM caffeine led to a sensitization enhancement ratio (at 10% survival) of 1.8 in p53(-/-) cells, but only 1.3 in wild-type (p53+/+) cells. Caffeine 34-42 tumor protein p53 Homo sapiens 155-158 8968086-6 1996 The differential sensitivity of p53(-/-) cells to X-rays and caffeine was thought to be due to override of the G2-M block to cell cycle progression. Caffeine 61-69 tumor protein p53 Homo sapiens 32-35 8968086-9 1996 However, for p53(-/-) cells, a greater proportion were in S phase after treatment with caffeine, and a complete loss of S-phase delay was observed after UV irradiation. Caffeine 87-95 tumor protein p53 Homo sapiens 13-16 8968086-11 1996 Greater sensitization of p53(-/-) cells to caffeine could be mediated via override of S-phase delay. Caffeine 43-51 tumor protein p53 Homo sapiens 25-28 8837615-6 1996 We demonstrate that abrogation of G2 arrest by caffeine-mediated activation of p34cdc2 kinase results in the selective sensitization of p53-deficient primary and tumor cells to irradiation-induced apoptosis. Caffeine 47-55 tumor protein p53 Homo sapiens 136-139 8964480-4 1996 Treatment of cells with caffeine decreased the p53wt content and increased the proportion of metaphases with chromosome breaks; however, it did not induce hyperdiploidy in the majority of cell lines. Caffeine 24-32 tumor protein p53 Homo sapiens 47-50 8692199-7 1996 Modification of endogenous and exogenous p53 expression by caffeine, which interferes with normal induction of p53 in response to DNA damage, showed no correlation between the induction of chromosome breaks and heteroploidy. Caffeine 59-67 tumor protein p53 Homo sapiens 41-44 8692199-7 1996 Modification of endogenous and exogenous p53 expression by caffeine, which interferes with normal induction of p53 in response to DNA damage, showed no correlation between the induction of chromosome breaks and heteroploidy. Caffeine 59-67 tumor protein p53 Homo sapiens 111-114 8692199-8 1996 We conclude that the caffeine- or mutant p53-induced increase in the frequency of chromosomal breaks in dividing LIM1215 cells is assonated with inactivation of wt-p53 function(s) responsible for control of G1 checkpoint and/or DNA repair, while numerical chromosome changes in these cells may be a result of elimination or modification of a separate p53 function, or due to gain-of-function activities of p53 mutants. Caffeine 21-29 tumor protein p53 Homo sapiens 41-44 8692199-8 1996 We conclude that the caffeine- or mutant p53-induced increase in the frequency of chromosomal breaks in dividing LIM1215 cells is assonated with inactivation of wt-p53 function(s) responsible for control of G1 checkpoint and/or DNA repair, while numerical chromosome changes in these cells may be a result of elimination or modification of a separate p53 function, or due to gain-of-function activities of p53 mutants. Caffeine 21-29 tumor protein p53 Homo sapiens 164-167 8692199-8 1996 We conclude that the caffeine- or mutant p53-induced increase in the frequency of chromosomal breaks in dividing LIM1215 cells is assonated with inactivation of wt-p53 function(s) responsible for control of G1 checkpoint and/or DNA repair, while numerical chromosome changes in these cells may be a result of elimination or modification of a separate p53 function, or due to gain-of-function activities of p53 mutants. Caffeine 21-29 tumor protein p53 Homo sapiens 164-167 8692199-8 1996 We conclude that the caffeine- or mutant p53-induced increase in the frequency of chromosomal breaks in dividing LIM1215 cells is assonated with inactivation of wt-p53 function(s) responsible for control of G1 checkpoint and/or DNA repair, while numerical chromosome changes in these cells may be a result of elimination or modification of a separate p53 function, or due to gain-of-function activities of p53 mutants. Caffeine 21-29 tumor protein p53 Homo sapiens 164-167 1933891-5 1991 Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Caffeine 0-8 tumor protein p53 Homo sapiens 66-69 1933891-5 1991 Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Caffeine 0-8 tumor protein p53 Homo sapiens 150-153 1933891-5 1991 Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Caffeine 215-223 tumor protein p53 Homo sapiens 66-69 1933891-5 1991 Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Caffeine 215-223 tumor protein p53 Homo sapiens 150-153