Resveratrol Induces Apoptosis in Murine Prostate Cancer Cells via Hypoxia-Inducible Factor 1-alpha (HIF-1α)/Reactive Oxygen Species (ROS)/P53 Signaling

Abstract

BackgroundResveratrol, a polyphenol found on the surface of red fruits, is able to suppress many kinds of malignancies. Nevertheless, its mechanism of action is not yet clear. Consequently, this study aimed to elucidate its influence and explore the etiology of PCCs (prostate cancer cells).Material/MethodsThe proliferation of prostate cancer cells was determined by CCK-8 assay. Cell apoptosis was determined by Hoechst staining FC assay. Cell migration was detected by scratch test. The levels of apoptosis-related protein were detected by Western blot analysis.ResultsIt was discovered that resveratrol suppresses cellular survival and migration and enhances cell death. In addition, it was revealed that resveratrol elevated ROS concentration and expression of biomarker of cell death Bax, while inhibiting Bcl2, an anti-apoptotic protein, and reinforcing expression of p53. Moreover, resveratrol remarkably increased the expressions of HIF-1α and p53 in PC cells. Resveratrol suppressed cell survival and promoted cell death, but its effects were reversed after HIF-1α knockdown, suggesting that the effects of resveratrol in PC are mediated via HIF-1α.ConclusionsOur findings indicate that resveratrol induces apoptosis via HIF-1α/ROS/p53 signaling in prostate cancer cells and may be a useful therapeutic agent against prostate cancer.

Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

“…Bcl2 is an important antiapoptotic protein in cells [19]. A large number of studies [20, 21] have shown that Bcl2 expression is significantly reduced while Bax and Caspase-3, the important proapoptotic factors [22], are increased during apoptosis. In this study, we found that crocin rescued the apoptosis of hippocampal CA1 cells and prefrontal cortical neurons of AD rats, demonstrated by decreased number of apoptosis cells, decreased Bcl-2 expression, and increased Bax and Caspase-3 expression when compared with AD rats.…”

The Power of Phytochemicals Combination in Cancer Chemoprevention

“…RE interferes with AKT activity and triggers apoptosis [143]. RE enhances p53 acetylation and apoptosis [144]. RE causes G1 arrest [145].…”

Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets

“…This article provides an overview of recent findings about the anti-PCa activity of different natural compounds (Figure 2, Table 1). [47][48][49][50][51][52][53][54]80,100,107,123,124,[135][136][137][138][139]161,163,164,186,190,191,212] The use of phytochemicals for PCa management offers several advantages. Firstly, natural products are safe and well tolerated, as well as usually economically affordable.…”

“…Indeed, while apigenin, luteolin, genistein, and celastrol inhibited the proteasomal activity and caused ubiquitinated protein accumulation in different PCa cell lines [154][155][156], quercetin, curcumin, silibinin, and tannic acid induced endoplasmic reticulum (ER) stress [157][158][159][160], a condition where unfolded/misfolded proteins accumulate in the ER lumen and promote the activation of distinct pro-death cascades, including the double-stranded RNA-dependent protein kinase PKR-like ER kinase (PERK)/eukaryotic initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) pathway and the inositol-requiring enzyme 1α (IRE1)/c-Jun N-terminal kinase (JNK)/p38 MAPK cascade [161]. Notably, curcumin-and silibinin-mediated ER stress was associated with generation of reactive oxygen species (ROS) and redox homeostasis alteration [159,162], which were also observed in resveratrol-and sulforaphane-treated PCa cells [163][164][165][166].…”