The Therapeutic Use of HIF Pathway Inhibitors to Reduce Castrate Resistant Prostate Cancer
INTRODUCTION: Prostate cancer (PC) is the leading cause of cancer related death of men in American, and castration resistant prostate cancer (CRPC) is the major mortality determinant; therefore, it has a lot of importance.1,2 Previous studies conducted have verified the importance of the hypoxia inducible factor (HIF) pathway in the progression of PC to CRPC by providing convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy.3,5,6 These studies have also shown the effect androgen deprivation therapy (ADT) induced hypoxia has on the transcriptional activity of HIF as an adaptive response.1,6 Resveratrol, a polyphenol found on the outside of red fruits, can stifle numerous sorts of malignancies including PC.3 By and by, its mechanism of action isn’t yet clear.3 Subsequently, this study meant to clarify its impact on PC cells.3 MATERIAL AND METHODS: The multiplication of prostate cancer cells was dictated by CCK-8 assay. Cell apoptosis was controlled by Hoechst staining folin-coicalteu assay. Cell migration was recognized by scratch test. The degrees of apoptosis-related protein were recognized by Western blot analysis. RESULTS: It was found that resveratrol suppresses cellular proliferation and migration and enhances cell death.3 What’s more, it was uncovered that resveratrol raised ROS concentration and the articulation of biomarker of cell death Bax, while repressing Bcl2, an anti-apoptotic protein, and strengthening expression of p53.3 Besides, resveratrol surprisingly increase the secretion of HIF-1α and p53 in PC cells.3 Resveratrol stifled cell proliferation and enhanced cell death, yet its effects were turned around after HIF-1α knockdown, suggesting that the impacts of resveratrol in PC are intervened by means of HIF-1α.3 CONCLUSION: The findings indicate that resveratrol induces apoptosis via HIF-1α/p53 signaling in prostate cancer cells and may be a useful therapeutic agent against prostate cancer. This therapeutic use is important given that a physician could prescribe a diet high in resveratrol in conjunction with other forms of therapy.
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