Alok De
Kansas City VA Medical Center, USA
Title: Anti-proliferative, anti-angiogenic and anti-metastatic effect of Emblica officinalis (Amla) on ovarian cancer cells via microRNA regulated and autophagy mechanisms
Biography
Biography: Alok De
Abstract
Ovarian cancer (OC), the most lethal gynecologic cancer, may be treated with surgery, chemotherapy and/or radiation therapy. None of these strategies are very effective. Recently, we have demonstrated that Emblica officinalis (Amla) extract (AE) has anti-neoplastic effect on OC cells in vitro and in mouse xenograft tumors. We hypothesized that anti-proliferative, anti-angiogenic and anti-metastatic effect of AE on OC cells via microRNA regulated and autophagy mechanism. The effects of AE on OC cells - OVCAR3, SKOV3, A2780cis and OC cells-derived mouse xenograft tumors were studied. The effect of AE on OC cells proliferation, migration and invasion was studied. Expression of - proangiogenic receptor- IGF1R, angiogenic marker- CD31, angiogenesis regulatory transcription factor- HIF-1α, metastasis-associated transcription factor- SNAIL1, adhesion protein- E-cadherin and autophagy proteins- beclin1 and LC3B-II in OC cells and mouse xenograft tumors were studied. Expression of microRNAs in OC cells and exosomes released from OC cells after AE treatment was studied. AE dose and time dependently inhibited cell proliferation, migration and invasiveness in OC cells. AE significantly reduced the expression of HIF-1α, IG1R, CD31and proliferating marker- Ki67 both in vitro and in vivo. AE reduced SNAIL1 and induced E-cadherin expression both in vitro and in vivo. AE significantly increased beclin1 and LC3B-II expression both in vitro and in vivo. AE significantly increased microRNA-375 expression in OC cells and in exosomes derived from OC cells. These studies suggest that AE inhibits OC cells growth via simultaneous activation of autophagy and miR-375, by targeting IGF1R, SNAIL1, down-regulating HIF-1α and inhibiting angiogenesis.