PMID-sentid	Pub_year	Sent_text		comp_official_name	comp_offsetprotein_name	organism	prot_offset
20460760-5	2010	A significantly elicited hypodiploid cell population was found in cells treated with 2, 4, and 8microM shikonin for 24 h. Moreover, treatment with shikonin induced reactive oxygen species (ROS) generation, increased extracellular signal-regulated kinase (ERK) phosphorylation, decreased B-cell lymphoma-2 (Bcl2) expression, and was accompanied by poly(ADP-ribose) polymerase (PARP) cleavage.	shikonin	103-111	BCL2 apoptosis regulator	Homo sapiens	287-304	
20460760-5	2010	A significantly elicited hypodiploid cell population was found in cells treated with 2, 4, and 8microM shikonin for 24 h. Moreover, treatment with shikonin induced reactive oxygen species (ROS) generation, increased extracellular signal-regulated kinase (ERK) phosphorylation, decreased B-cell lymphoma-2 (Bcl2) expression, and was accompanied by poly(ADP-ribose) polymerase (PARP) cleavage.	shikonin	103-111	BCL2 apoptosis regulator	Homo sapiens	306-310	
34321365-5	2022	Moreover, shikonin enhanced mitochondrial membrane depolarization and Bax expression and also decreased Bcl-2 expression with translocation of cytochrome c from mitochondria into the cytosol.	shikonin	10-18	BCL2 apoptosis regulator	Homo sapiens	104-109	
19027226-2	2009	Here, we show that the naturally-occurring shikonin analogues (deoxyshikonin, acetylshikonin, isobutyrylshikonin, beta,beta-dimethylacrylshikonin, isovalerylshikonin, alpha-methyl-n-butylshikonin) could bypass drug resistance mediated by not only P-gp, Bcl-2, and Bcl-xL, but also two additional important drug-resistant factors MRP1 and BCRP1, by induction of necroptosis.	shikonin	43-51	BCL2 apoptosis regulator	Homo sapiens	253-258	
34504572-14	2021	Furthermore, shikonin significantly decreased caspase-9 and caspase-3 activities, increased Bcl-2 expression and decreased Bax and cytochrome c expression levels in H2O2-induced HT29 cells.	shikonin	13-21	BCL2 apoptosis regulator	Homo sapiens	92-97	
34646528-9	2021	Shikonin reversed the expression of the inflammatory cytokines TNF-alpha and IL-1beta and apoptosis-related molecules Bax, Bcl-2, and cleaved caspase 3 in LPS-induced NP cells.	shikonin	0-8	BCL2 apoptosis regulator	Homo sapiens	123-128	
15453709-0	2004	Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2 family, p27, and p53, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells.	shikonin	26-34	BCL2 apoptosis regulator	Homo sapiens	74-79	
15453709-6	2004	Here, we found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L), while shikonin had little effect on the levels of Bax protein.	shikonin	20-28	BCL2 apoptosis regulator	Homo sapiens	134-139	
29449346-5	2018	Moreover, shikonin-induced apoptosis was characterized by the up-regulation of the pro-apoptotic proteins cleaved-Caspase-3 and Bax, and the down-regulation of the anti-apoptotic protein Bcl-2.	shikonin	10-18	BCL2 apoptosis regulator	Homo sapiens	187-192	
32536866-18	2020	Further study showed that shikonin decreased the levels of STAT3-targeted genes Mcl-1, Bcl-2, MMP-2, vimentin, and Twist, which are involved in melanoma survival, migration, and invasion.	shikonin	26-34	BCL2 apoptosis regulator	Homo sapiens	87-92	
29925224-5	2019	Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3.	shikonin	0-8	BCL2 apoptosis regulator	Homo sapiens	130-153	
29925224-5	2019	Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3.	shikonin	0-8	BCL2 apoptosis regulator	Homo sapiens	173-178	
30594131-7	2018	Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid.	shikonin	24-32	BCL2 apoptosis regulator	Homo sapiens	160-165	
31452796-9	2019	In summary, shikonin can sensitize esophageal cancer cells to paclitaxel-treatment by promoting cell mitotic arrest and reinforcing the susceptibility of esophageal cancer cells to apoptosis induced by paclitaxel, which is potentially associated with altered levels of Bcl-2 and p53.	shikonin	12-20	BCL2 apoptosis regulator	Homo sapiens	269-274	
25879420-10	2015	Shikonin also induced the mitochondrial apoptotic pathway mediated through the enhanced expression of the pro-apoptotic Bax and inhibition of Bcl-2, disruption of the mitochondrial membrane potential (MMP) followed by the activation of caspase-9, caspase-3, and PARP cleavage.	shikonin	0-8	BCL2 apoptosis regulator	Homo sapiens	142-147	
26235879-3	2015	Shikonin-induced apoptosis was associated with activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, up-regulation of p73, and down-regulation of BCL-2.	shikonin	0-8	BCL2 apoptosis regulator	Homo sapiens	162-167	
25669168-9	2015	Finally, in response to shikonin treatment, Mcl-1 and Bcl-2 levels increased in the scrambled control cells treated with shikonin, whereas Bcl-2 decreased and Mcl-1 slightly increased in the GRP78KD PC-3 cells.	shikonin	24-32	BCL2 apoptosis regulator	Homo sapiens	54-59	
25669168-9	2015	Finally, in response to shikonin treatment, Mcl-1 and Bcl-2 levels increased in the scrambled control cells treated with shikonin, whereas Bcl-2 decreased and Mcl-1 slightly increased in the GRP78KD PC-3 cells.	shikonin	24-32	BCL2 apoptosis regulator	Homo sapiens	139-144	
25720435-4	2015	In addition, shikonin evidently induced apoptosis due to decreasing Bcl-2 expression, increasing Bax expression, activating caspase and inactivating NF-kappaB, while pretreatment with a pan-caspase inhibitor Z-Asp-CH2-DCB abrogated shikonin-induced apoptosis.	shikonin	13-21	BCL2 apoptosis regulator	Homo sapiens	68-73	
22446899-9	2012	Moreover, shikonin causes catalase downregulation and SOD-1 upregulation as well as decreased Bcl-2 and increased Bax expression.	shikonin	10-18	BCL2 apoptosis regulator	Homo sapiens	94-99	
24962386-8	2014	In addition, the treatment of shikonin in HLEs significantly increased the ratio of Bax/Bcl-2, disrupted mitochondria membrane potential (MMP) and activated caspases.	shikonin	30-38	BCL2 apoptosis regulator	Homo sapiens	88-93	
25591861-10	2015	Further investigation revealed that Shikonin induces apoptosis in scar fibroblasts by differentially regulating the expression of caspase 3, Bcl-2, phospho-Erk1/2 and phospho-p38.	shikonin	36-44	BCL2 apoptosis regulator	Homo sapiens	141-146