Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3PT platinum-resistant human ovarian cancer cells

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 SKOV3(PT) platinum-resistant human ovarian cancer cells and observed that TPL activated caspase 3 and induced the dose-dependent apoptosis of the SKOV3(PT) 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)-kappa B 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-kappa B 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-kappa B pathway through mitochondria-derived ROS accumulation, promoting the apoptosis of the SKOV3(PT) 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.