Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been established that signal transducer and activator of transcription 3 serves as an oncoprotein in various human cancers; targeting it is therefore a reasonable approach for emerging cancer therapies. Cryptotanshinone, a natural compound extracted from the root of Salvia miltiorrhiza Bunge, has been identified as a potential STAT3 inhibitor. However, its functional role in renal cell carcinomas remains largely unknown. Therefore, we investigated the mode of action for cryptotanshinone. We found that cryptotanshinone substantially suppressed cancer cell growth while it promoted cell apoptosis by inhibiting the phosphorylation of STAT3 at Tyr705 and its blocking nuclear translocation. Coordinately, P-AKT, CyclinD1, C-MYC, MEKK2, and HGF were down-regulated and cell cycle progression was arrested at the G0/G1 phase, thereby attenuating cell proliferation. Moreover, the level of Cleaved-Caspase-3 was elevated while Bcl-2 and Survivin were down-regulated, accounting for the increased apoptosis. Furthermore, in vivo results revealed that cryptotanshinone effectively inhibits tumorigenesis in an A498-xenografted mouse model. Taken together, our data gives a more comprehensive understanding of how cryptotanshinone functions in renal cell carcinomas and demonstrates its potential as a powerful therapeutic approach to treat renal cell carcinomas.
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PMID:Cryptotanshinone inhibits proliferation yet induces apoptosis by suppressing STAT3 signals in renal cell carcinoma. 2865 2

Mixed-lineage kinase 3 (MLK3), the mitogen-activated protein kinase kinase kinase (MAP3K), has been recognized as a player in tumorigenesis and oncogenic signalling, yet its detailed functions and signalling in cervical cancer have not been fully elucidated. Here, we identify that cervical cancer cells display higher mRNA and protein levels of MLK3 than normal cervical epithelial squamous cells. In HeLa and SiHa cell, MLK3 knockdown using siRNA remarkably suppressed cell survival and promoted cell apoptosis, with increased expression of the apoptosis-related protein Bax and reduced Bcl-2. Moreover, MLK3 knockdown promoted cell autophagy, demonstrated by increased ratio of autophagy-related proteins LC3II/LC3I and decreased p62 expression in MLK3 depletion cells. Furthermore, MLK3 knockdown remarkably abolished Notch-1 expression in cervical cancer cells. By co-treating Hela cells with MLK3 specific siRNA and pcDNA3.1-Notch-1 overexpression plasmid or autophagy inhibitor 3-MA, we found that MLK3 played its role in cervical cancer cells via the Notch-1/autophagy network. Our results demonstrate the importance of MLK3 in cervical cancer progression via modulating the Notch-1/autophagy network, and suggest that MLK3 is a promising therapeutic target for cervical cancer.
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PMID:MLK3 silence induces cervical cancer cell apoptosis via the Notch-1/autophagy network. 3119 72


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