We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-KB pathway in SKOV3<sup>PT</sup> platinum-resistant human ovarian cancer cells.
- Authors
YAN-YING ZHONG; HE-PING CHEN; BU-ZHEN TAN; HAI-HONG YU; XIAO-SHAN HUANG
- 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 SKOV3PT platinum-resistant human ovarian cancer cells and observed that TPL activated caspase 3 and induced the dose-dependent apoptosis of the SKOV3PT cells. 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-KB 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-KB 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-KB pathway through mitochondria-derived ROS accumulation, promoting the apoptosis of the SKOV3PT cells. 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.
- Subjects
REACTIVE oxygen species; NF-kappa B; DRUG resistance in cancer cells; OVARIAN cancer; TRIPTOLIDE
- Publication
Oncology Letters, 2013, Vol 6, Issue 4, p1084
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2013.1524