Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells
| العنوان: | Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells |
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| المؤلفون: | Jueun Kim, Kyoung-Hwa Seo, In-Sung Song, Choung-Soo Kim, Sung-Wuk Jang, Nam-In Baek, Yunlim Kim, Yu Jeong Jeong |
| المصدر: | Cellular and Molecular Life Sciences. 77:4663-4673 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Programmed cell death, bcl-X Protein, Down-Regulation, Mice, Nude, Antineoplastic Agents, Bcl-xL, urologic and male genital diseases, TMPRSS2, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, Downregulation and upregulation, Cell Line, Tumor, LNCaP, Animals, Humans, Molecular Biology, Cell Proliferation, Membrane Potential, Mitochondrial, Pharmacology, 0303 health sciences, Cell Death, biology, Chemistry, 030302 biochemistry & molecular biology, Prostate, Prostatic Neoplasms, Cell Biology, Prostate-Specific Antigen, Saponins, Gene Expression Regulation, Neoplastic, Androgen receptor, Disease Models, Animal, Cytosol, Receptors, Androgen, Cell culture, PC-3 Cells, Androgens, biology.protein, Cancer research, Molecular Medicine, Female, Reactive Oxygen Species |
| الوصف: | The androgen receptor (AR) plays an important role in the pathogenesis and development of prostate cancer (PCa). Mostly, PCa progresses to androgen-independent PCa, which has activated AR signaling from androgen-dependent PCa. Thus, inhibition of AR signaling may be an important therapeutic target in androgen-dependent and castration-resistant PCa. In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponin treatment decreases B-cell lymphoma-extra large (Bcl-xL) and mitochondrial membrane potential, thereby increasing the release of cytochrome c into the cytosol. Moreover, Bcl-xL inhibition and subsequent mitochondria-mediated cell death caused by S-saponin were reversed by Bcl-xL or AR overexpression. Interestingly, S-saponin-mediated cell death was significantly reduced by a reactive oxygen species (ROS) scavenger, N-acetylcystein. Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential. |
| تدمد: | 1420-9071 1420-682X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f83f170931aa2cc855893ec6ddc09d4cTest https://doi.org/10.1007/s00018-019-03429-2Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....f83f170931aa2cc855893ec6ddc09d4c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14209071 1420682X |
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