Growth inhibitory effects of 3'-hydroxypterostilbene in human prostate cancer cells and xenograft mice

Prostate cancer is the second highest cause of cancer-related death among men in the United States. Most of these deaths are caused by invasive and metastatic spread of the prostate cancer. Therefore, more efforts should be dedicated to the development of preventive strategies to reduce prostate cancer prevalence and impact. Pterostilbene (Pt) is a natural antioxidant compound predominantly found in blueberries, grapes and a tree wood, Pterocarpus marsupium. 3'-Hydroxypterostilbene (OHPt), one of hydroxyl analogs of pterostilbene, can be isolated from whole plant of the herb Sphaerophysa salsula, a shrub widely distributed in central Asia and northwest China. The objective of this study was to investigate the growth inhibitory effects of 3'-hydroxypterostilbene on human prostate cancer cells in vitro and in vivo. The results showed that OHPt significantly decreased cell viability of PC-3 and LNCaP cells in a dose- and time-dependent manner. However, OHPt showed much stronger inhibitory effects on the growth of the prostate cancer cells in comparison with its parent compound Pt, suggesting that addition of an OH group to the 3’-position of Pt ameliorated its anti-cancer cell proliferative activity. Next, we further elucidated the molecular mechanisms of anti-proliferation of human prostate cancer cells by OHPt. Treatment with OHPt induced apoptosis via disruption of mitochondrial membrane integrity and activation of caspase-8, caspase-9 and caspase-3 in both PC-3 and LNCaP cells. Moreover, OHPt increased the ratio of proapototic protein Bax to anti-apoptotic protein Bcl-xL. These findings suggested that OHPt had a strong growth inhibitory effect on PC-3 and LNCaP cells through induction of intrinsic and extrinsic apoptotic pathway. Besides, OHPt induced autophagic cell death by upregulating the expression of Beclin-1, LC3 proteins and autophagosome formation. Furthermore, in vivo study, OHPt showed potent anti-tumor effects in PC-3 xenograft nude mice. Treatment of mice with OHPt efficiently inhibited the tumor volume and tumor weight. Taken together, the findings of this research provide insights that OHPt might have significant chemotherapeutic applications for the future management of prostate cancer.Ph.D.Includes bibliographical referencesby Hui-Yun Tsa