Platinum‐based combination chemotherapy triggers cancer cell death through induction of BNIP3 and ROS, but not autophagy
| Autor: | Guang Huan Sun, Kai Chi Yang, Shye Jye Tang, Ling Yen Chung, Kuang Hui Sun, Yi Ching Wu, Hui Ju Huang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
autophagy Programmed cell death Lung Neoplasms BNIP3 Antineoplastic Agents Models Biological 03 medical and health sciences 0302 clinical medicine Proto-Oncogene Proteins medicine Humans Lung cancer Platinum reactive oxygen species Cisplatin combination chemotherapy Cell Death business.industry Adenine Autophagy Membrane Proteins Cancer Combination chemotherapy Original Articles Cell Biology Cell cycle medicine.disease Mitochondria Protein Transport 030104 developmental biology A549 Cells 030220 oncology & carcinogenesis Mitochondrial Membranes Cancer cell Cancer research Molecular Medicine Original Article Drug Therapy Combination business medicine.drug |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.14898 |
| Popis: | These days, cancer can still not be effectively cured because cancer cells readily develop resistance to anticancer drugs. Therefore, an effective combination of drugs with different mechanisms to prevent drug resistance has become a very important issue. Furthermore, the BH3‐only protein BNIP3 is involved in both apoptotic and autophagic cell death. In this study, lung cancer cells were treated with a chemotherapy drug alone or in combination to identify the role of BNIP3 and autophagy in combination chemotherapy for treating cancer. Our data revealed that various combinational treatments of two drugs could increase cancer cell death and cisplatin in combination with rapamycin or LBH589, which triggered the cell cycle arrest at the S phase. Cells with autophagosome and pEGFP‐LC3 puncta increased when treated with drugs. To confirm the role of autophagy, cancer cells were pre‐treated with the autophagy inhibitor 3‐methyladenine (3‐MA). 3‐MA sensitized cancer cells to chemotherapy drug treatments. These results suggest that autophagy may be responsible for cell survival in combination chemotherapy for lung cancer. Moreover, BNIP3 was induced and localized in mitochondria when cells were treated with drugs. The transfection of a dominant negative transmembrane deletion construct of BNIP3 (BNIP3ΔTM) and treatment of a reactive oxygen species (ROS) inhibitor suppressed chemo drug‐induced cell death. These results indicate that BNIP3 and ROS may be involved in combination chemo drug‐induced cell death. However, chemo drug‐induced autophagy may protect cancer cells from drug cytotoxicity. As a result, inhibiting autophagy may improve the effects of combination chemotherapy when treating lung cancer. |
| Databáze: | OpenAIRE |
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