Abstract
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. Citation Format: Mai F. Tolba, Hany A. Omar. Insights into the anti-prostate cancer activity of pterostilbene. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B45.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
