title: A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways.
abstract: BACKGROUND
  Phyllanthus 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Corilagin 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.
  
  
  CONCLUSIONS
  Corilagin 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.
authors: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, People's Republic of China.
authors: Luoqi
authors: L
authors: Jia
authors: Hongyan
authors: H
authors: Jin
authors: Jiayi
authors: J
authors: Zhou
authors: Lianghua
authors: L
authors: Chen
authors: Yiling
authors: Y
authors: Lu
authors: Yanlin
authors: Y
authors: Ming
authors: Yinhua
authors: Y
authors: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D047348:Hydrolyzable Tannins; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D029803:Phyllanthus / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056744:Cyclin B1; D005960:Glucosides; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C049096:corilagin; D017239:Paclitaxel