Abstract
BackgroundPhyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells.MethodsThe ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts.ResultsCorilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 μM, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 μM. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-β secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-β-induced stabilization of Snail. In contrast, a reduction of TGF-β secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-β secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways.ConclusionsCorilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-β/AKT/ERK/Smad signaling pathways.
Highlights
Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb
Corilagin inhibits the growth of ovarian cancer cell lines in vitro and in vivo Ovarian cancer cell lines (Hey, SKOv3ip, and HO8910PM) and normal ovarian surface epithelial (OSE) cells (OSE01, OSE02, and OSE03) were used to examine the effects of Corilagin in cell culture
Using an ELISA, we found that most ovarian cancer cell lines secrete TGF-β1 into cell culture supernatants, and this secretion increased as the growth rate increased
Summary
We identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. (P. niruri L.) belongs to the Euphorbiaceae family and originated in India It usually occurs as a winter weed throughout the tropic and subtropic parts of the globe, including China, South Asia, and America. P. niruri L. is a popular folk medicine for treating nephritic, urocystic, gastrointestinal, and hepatic infections. It has traditionally been used in antiviral, antioxidant, anti-inflammatory, and antidiabetic treatments as well as for radiation protection. Our recent work identified that Corilagin is a major active compound from P. niruri L. extracts; it is effective in retarding the growth of hepatocarcinoma cells [unpublished data, Ming et al.]
Sign-in/Register to view highlights & summary 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.
