title: Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells.
abstract: Ginkgolide B (GB), the primary active component ofGinkgo bilobaextracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cong
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Gynecologic Oncology and Epidemiology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA xucongjian@gmail.com bye@yahoo.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, P.R. China Municipal Key Laboratory for Diseases Related to Women's Reproductive and Endocrine Systems, Fudan University, Shanghai, P.R. China Institute of Biomedical Sciences, Fudan University, Shanghai, P.R. China xucongjian@gmail.com bye@yahoo.com.
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B; D002945:Cisplatin