Rubus coreanus Miquel extract causes apoptosis of doxorubicin-resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation
| Autor: | Seong-Gyu Ko, Sung-Gook Cho, Min Kyoung Kim, Hyeong Sim Choi, Yong Cheol Shin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research MAP Kinase Kinase 4 Apoptosis Biology NCI/ADR-RES Biochemistry 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Genetics Humans Viability assay Phosphorylation Molecular Biology Protein kinase B Ovarian Neoplasms Plant Extracts Kinase Cell cycle Neoplasm Proteins 030104 developmental biology Oncology chemistry Doxorubicin Drug Resistance Neoplasm Cancer cell Cancer research Molecular Medicine Female Rubus Ellagic acid |
| Zdroj: | Molecular Medicine Reports. 13:4065-4072 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2016.4996 |
| Popis: | Cancer cells can acquire an anticancer, drug-resistant phenotype following chemotherapy, which is tightly linked to cancer malignancy and patient survival rates. Therefore, the identification of options to treat chemotherapy‑resistant cancer cells is an urgent requirement. Rubus coreanus Miquel (RCM) has long been used as a source of food. In addition, it has been reported that RCM has effective functions against particular diseases, including cancer and inflammation. In the present study, it was demonstrated that RCM extract caused the apoptotic cell death of doxorubicin‑resistant NCI/ADR‑RES ovarian cancer cells by phosphorylating c‑Jun N‑terminal kinase (JNK). The RCM‑mediated reduction of cell viability showed no synergism with doxorubicin. In addition, ellagic acid and quercetin, which are phytochemicals found in RCM, also caused apoptosis of the NCI/ADR‑RES cells. In subsequent investigations of the RCM‑altered signaling pathway, RCM extract, ellagic acid and quercetin were found to commonly induce the phosphorylation of JNK and AKT. Additionally, the inhibition of JNK with SP600125 repressed the apoptotic cell death induced by RCM extract, ellagic acid and quercetin, and the inhibition of JNK appeared to switch apoptosis to necrosis. JNK inhibition also reduced the phosphorylation of AKT, which was induced by RCM extract, ellagic acid and quercetin, suggesting that the phosphorylation of JNK is required for AKT phosphorylation in RCM‑, ellagic acid‑ or quercetin‑induced apoptotic cell death. Therefore, the data obtained in the present study led to the conclusion that RCM caused apoptosis of doxorubicin‑resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation, and suggested that RCM may be effective in the treatment of chemotherapy‑resistant cancer cells. |
| Databáze: | OpenAIRE |
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