Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3PT platinum-resistant human ovarian cancer cells
| Autor: | He‑Ping Chen, Yan‑Ying Zhong, Xiao‑Shan Huang, Bu‑Zhen Tan, Hai‑Hong Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cisplatin
chemistry.chemical_classification reactive oxygen species Cancer Research Reactive oxygen species business.industry nuclear factor-κB Caspase 3 Articles Triptolide Inhibitor of apoptosis platinum resistance XIAP chemistry.chemical_compound Mitochondrial respiratory chain ovarian cancer Oncology chemistry Apoptosis triptolide Immunology Cancer research medicine business medicine.drug |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | 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)-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 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. |
| Databáze: | OpenAIRE |
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