α-Viniferin activates autophagic apoptosis and cell death by reducing glucocorticoid receptor expression in castration-resistant prostate cancer cells.
Kejun ChengXi LiuLu ChenJian-Min LvFa-Jun QuXiu-Wu PanLin LiXin-Gang CuiYi GaoDan-Feng XuPublished in: Medical oncology (Northwood, London, England) (2018)
Prostate cancer (PCa) is one of the most commonly diagnosed urological malignancies. However, there are limited therapies for PCa patients who develop biochemical recurrence after androgen deprivation therapy (ADT). In the present study, we investigated the therapeutic efficacy and mechanism of α-Viniferin (KCV), an oligostilbene of trimeric resveratrol, against human PCa cells and found that it markedly inhibited the proliferation of LNCaP, DU145, and PC-3 cancer cells in a time- and dose-dependent manner, and had a strong cytotoxicity in non-androgen-dependent PCa cells. In addition, KCV inhibited AR downstream expression in LNCaP cells, and inhibited activation of GR signaling pathway in DU145 and PC-3. Further investigation indicated that KCV could induce cancer cell apoptosis through AMPK-mediated activation of autophagy, and inhibited GR expression in castration-resistant prostate cancer(CRPC). These findings suggest that KCV may prove to be a novel and effective therapeutic agent for the treatment of CRPC.
Keyphrases
- cell cycle arrest
- cell death
- induced apoptosis
- signaling pathway
- prostate cancer
- endoplasmic reticulum stress
- pi k akt
- poor prognosis
- squamous cell carcinoma
- endothelial cells
- epithelial mesenchymal transition
- cell proliferation
- skeletal muscle
- radical prostatectomy
- mesenchymal stem cells
- young adults
- high resolution
- smoking cessation
- urinary tract