title: Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3PTplatinum-resistant human ovarian cancer cells.
abstract: An acquired resistance to platinum-based drugs has emerged as a significant impediment to effective ovarian cancer therapy. The present study explored the anticancer mechanisms of triptolide (TPL) in SKOV3PTplatinum-resistant human ovarian cancer cells and observed that TPL activated caspase 3 and induced the dose-dependent apoptosis of the SKOV3PTcells. Furthermore, TPL inhibited complex I of the mitochondrial respiratory chain (MRC) followed by an increase of reactive oxygen species (ROS), which further inhibited nuclear factor (NF)-κB activation and resulted in the downregulation of anti-apoptotic proteins, Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP). Notably, the pre-treatment with N-acetyl-L-cysteine (NAC) abolished the TPL-induced ROS generation, NF-κB inhibition and cell apoptosis, but did not affect the inhibitory effect of TPL on complex I activity. These results suggested that TPL negatively regulated the NF-κB pathway through mitochondria-derived ROS accumulation, promoting the apoptosis of the SKOV3PTcells. Furthermore, TPL synergistically enhanced the cytotoxicity of cisplatin against platinum-resistant ovarian cancer cells. Collectively, these findings suggest that TPL is able to overcome chemoresistance and that it may be an effective treatment for platinum-resistant ovarian cancer, either alone or as an adjuvant therapy.
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China ; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Zhong
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Chen
authors.forename: Bu-Zhen
authors.initials: BZ
authors.lastname: Tan
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Yu
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Huang
keywords: nuclear factor-κB; ovarian cancer; platinum resistance; reactive oxygen species; triptolide