Hany A. Omar
University of Sharjah, United Arab of Emirates
Title: Anti-prostate Cancer Activity of Pterostilbene
Biography
Biography: Hany A. Omar
Abstract
Castration-resistant prostate cancer (PC) is one of the most challenging cancers with limited therapeutic options. Angiogenesis is a key mechanism required for the progression of advanced metastatic stage of PC. Interference with angiogenesis halts prostate tumor progression and metastases. Estrogen receptor alpha (ER-α) is upregulated in PC compared to normal tissues. ER-α is implicated in tumor angiogenesis through activating vascular endothelial growth factor (VEGF) transcription. Pterostilbene (PT) is an active component of blueberries that exhibits anti-proliferative and antimetastatic effects in PC. The impact of PT on pro-angiogenic signals is not known. The current study tested the hypothesis that PT exhibits sensitizes prostate cancer (PC) cells to chemotherapy. We also examined the underlying mechanisms by which PT exhibits cytotoxic effects in PC with special emphasis on ER-α, Akt activity and angiogenesis signals. PT is cytotoxic against LNCaP, DU-145 and PC-3 with IC50 of 33.76, 41.17 and 58.9 µM. PT synergized doxorubicin in both LNCaP and PC-3 cells. Molecular docking indicated that PT interacts with ER-α active site with a comparable affinity to estradiol. Since, ER-α is implicated in the progression of PC. The effect of PT on PC migration and invasion was investigated and results showed significant reduction in both functions. PT suppressed ER-α expression, ER-α(Ser-167) and Akt(Ser473) phosphorylations in PC-3 cells. PT opposed the release of the pro-angiogenic growth factors VEGF, IGF-1 and TGF-β by 41.5, 36.5 and 28.8% (P<0.05). Our findings suggest that PT could serve as a promising antiangiogenic therapy/ adjuvant for the management of advanced stage PC