Abstract 1931: A potential antitumor herb medicine, Corilagin, inhibits ovarian cancer cell growth by blockage of TGF-β/AKT/ERK signaling pathways

Abstract

Abstract Recently, we have identified that Corilagin is a major anti-tumor active component extracted from a well-known hepatoprotective and antiviral medicinal herb, Phyllanthus niruri L. Corilagin distinctly inhibited the growth of ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM, with IC50s less than 20µg/ml, while displayed the low toxicity against normal ovarian surface epithelium (OSE), with IC50s around 100µg/ml. Corilagin induced cell cycle arrest at G2 stage and enhanced apoptosis in Hey cancer cells. To explore its anti-tumor activity in vivo, Corilagin was delivered intra-peritoneally to the mice bearing SKOv3ip xenograft. Although no statistical difference observed on mice weight between untreated and Corilagin treated groups, xenograft tumor growth was significantly restarted by 15µg/mL of Corilagin treated group comparing to untreated control group (p<0.05). To understand the anti-tumor mechanisms of Corilagin, we performed reverse phase protein array (RPPA) analysis using untreated and Corilagen treated HO-8910PM cells, and the results were confirmed by Western blots. We have found that Corilagin blocked the activation of multiple signaling cascades, such as, pAKT and pERK. Particularly, Corilagin inhibits TGF-β secretion in the culture supernatant of all tested ovarian cancer cell lines and blocks the stabilization of Snail induced by TGF-β in HO-8910PM cells. In contrast, reduction of TGF-β secretion was not observed in cytotoxic drug Taxol-treated cancer cells, suggesting that Corilagin specifically targets TGF-β secretion. TGF-β signaling plays a critical role in epithelial-mesenchymal transition (EMT) and cancer metastasis. High concentration of TGF-β had been detected in ascites, blood and other body fluids of ovarian cancer patients. In addition, our recent studies identified that TGF-β being the most important inflammation factor in ovarian cancer, which stabilizes at the protein level of Snail, an inducer of EMT, and further enhanced Snail expression when combined with other inflammation factors. TGF-β is regulated by Smads, but could also be regulated by AKT/ERK signaling pathways. Our observations indicate that Corilagin extracted from Phyllanthus niruri L. acts as an effective natural targeted therapeutic agent against the growth of ovarian cancer cells via TGF-β/AKT/ERK signaling pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1931. doi:1538-7445.AM2012-1931