title: Protoapigenone, a novel flavonoid, inhibits ovarian cancer cell growth in vitro and in vivo.
abstract: Flavonoids are polyphenolic compounds and capable of inhibiting the growth of human cancer cells. Protoapigenone, a novel flavonoid, was isolated from the whole plant Thelypteris torresiana (Gaud), a native fern in Taiwan. In the present study, we explored the cytotoxic effects of protoapigenone on ovarian cancer cells and the immortalized ovarian epithelial cells by XTT assay. The effects of protoapigenone on cell cycle progression and apoptosis were also analyzed by FACS analysis, immunofluorescence study and immunoblotting analysis. The anti-ovarian cancer effect of protoapigenone was further examined using nude mice xenograft assay and immunohistochemistry. Our results showed that protoapigenone had a significant cytotoxicity on human ovarian cancer cells MDAH-2774 and SKOV3 but not on the immortalized non-cancer ovarian epithelial cells HOSE 6-3 and HOSE 11-12. Protoapigenone arrested MDAH-2774 and SKOV3 cells at S and G2/M phases via decreasing the expression of p-Cdk2, Cdk2, p-Cyclin B1 and Cyclin B1, as well as increasing the expression of inactive p-Cdc25C. Besides, protoapigenone had an enhanced cytotoxicity on SKOV3 cells enriched at S and G2/M phases, and ability to induce apoptosis through decreasing the protein levels of Bcl-xL and Bcl-2 and increasing the cleaved PARP by activating caspase-3. In nude mice study, protoapigenone treatment significantly suppressed the tumor growth, without major side effects. Taken together, protoapigenone showed a significant anti-ovarian cancer activity with low toxicity, suggesting its potential to be developed as a chemotherapeutic agent.
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Chang
authors.forename: Jinu-Huang
authors.initials: JH
authors.lastname: Su
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lee
authors.forename: Huey-May
authors.initials: HM
authors.lastname: Chen
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003512:Cyclohexanones / Q000627:therapeutic use*; D005260:Female; D047309:Flavones / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D003512:Cyclohexanones; D047309:Flavones; C524112:protoapigenone; D002945:Cisplatin