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JS-K, a nitric oxide pro-drug, regulates growth and apoptosis through the ubiquitin-proteasome pathway in prostate cancer cells

التفاصيل البيبلوغرافية
العنوان: JS-K, a nitric oxide pro-drug, regulates growth and apoptosis through the ubiquitin-proteasome pathway in prostate cancer cells
المؤلفون: Sai Zhang, Mingning Qiu, Longzhi Ke, Guobin Tan, Jianjun Liu, Lieqian Chen
المصدر: BMC Cancer
BMC Cancer, Vol 17, Iss 1, Pp 1-10 (2017)
سنة النشر: 2016
مصطلحات موضوعية: 0301 basic medicine, Male, Cancer Research, Proteasome Endopeptidase Complex, Proliferation, Caspase 3, SIAH2, Antineoplastic Agents, Apoptosis, Nitric Oxide, lcsh:RC254-282, Piperazines, 03 medical and health sciences, Ubiquitin, Cell Line, Tumor, Genetics, Humans, Prodrugs, Caspase, Cell Proliferation, Prostate cancer, Ubiquitin E3 ligase, biology, JS-K, Prostatic Neoplasms, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Molecular biology, Ubiquitin ligase, Cell biology, 030104 developmental biology, Oncology, Proteasome, biology.protein, Mdm2, Azo Compounds, Signal Transduction, Research Article
الوصف: Background In view of the fact that JS-K might regulate ubiquitin E3 ligase and that ubiquitin E3 ligase plays an important role in the mechanism of CRPC formation, the goal was to investigate the probable mechanism by which JS-K regulates prostate cancer cells. Methods Proliferation inhibition by JS-K on prostate cancer cells was examined usingCCK-8 assays. Caspase 3/7 activity assays and flow cytometry were performed to examine whether JS-K induced apoptosis in prostate cancer cells. Western blotting and co-immunoprecipitation analyses investigated JS-K’s effects on the associated apoptosis mechanism. Real time-PCR and Western blotting were performed to assess JS-K’s effect on transcription of specific AR target genes. Western blotting was also performed to detect Siah2 and AR protein concentrations and co-immunoprecipitation to detect interactions of Siah2 and AR, NCoR1 and AR, and p300 and AR. Results JS-K inhibited proliferation and induced apoptosis in prostate cancer cells. JS-K increased p53 and Mdm2 concentrations and regulated the caspase cascade reaction-associated protein concentrations. JS-K inhibited transcription of AR target genes and down-regulated PSA protein concentrations. JS-K inhibited Siah2 interactions and also inhibited the ubiquitination of AR. With further investigation, JS-K was found to stabilize AR and NCoR1 interactions and diminish AR and p300 interactions. Conclusions The present results suggested that JS-K might have been able to inhibit proliferation and induce apoptosis via regulation of the ubiquitin-proteasome degradation pathway, which represented a promising platform for the development of new compounds for PCa treatments. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3351-0) contains supplementary material, which is available to authorized users.
تدمد: 1471-2407
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76fae25f3f7dfd3be4045b8c1cc5d5da
https://pubmed.ncbi.nlm.nih.gov/28549433
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....76fae25f3f7dfd3be4045b8c1cc5d5da
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712407