Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction
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| Název: | Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction |
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| Autoři: | Jae-Youn Yi, Yun-Han Lee, Lee Hj, Ha-Na Choi, Seok-Il Hong, Tae-Boo Choe, In-Chul Park, Sang-Gu Hwang, Sung-Keum Seo, Jae-Hee Kim |
| Přispěvatelé: | Sung-Keum Seo, Jae-Hee Kim, Ha-Na Choi, Tae-Boo Choe, Seok-Il Hong, Jae-Youn Yi, Sang-Gu Hwang, Hyun-Gyu Lee, Yun-Han Lee, In-Chul Park, Lee, Yun Han, Lee, Hyun Gyu |
| Zdroj: | Biochemical and Biophysical Research Communications. 449:490-495 |
| Informace o vydavateli: | Elsevier BV, 2014. |
| Rok vydání: | 2014 |
| Témata: | 0301 basic medicine, Ionizing, Twist-Related Protein 1/biosynthesis, Mitochondria dysfunction, TWIST1, Acetylcysteine/pharmacology, Nuclear Proteins/biosynthesis, Membrane Potential, Arsenicals, Non-Small-Cell Lung/metabolism, 03 medical and health sciences, Arsenic Trioxide, Cell Death/drug effects, Reactive Oxygen Species/metabolism, Arsenic trioxide, Carcinoma, Non-Small-Cell Lung, Radiation, Ionizing, Non-Small-Cell Lung/radiotherapy, Humans, RNA, Small Interfering, Membrane Potential, Mitochondrial, Nuclear Proteins/genetics, Radiation, Cell Death, Carcinoma, Twist-Related Protein 1, Mitochondrial/drug effects, Small Interfering/pharmacology, Nuclear Proteins, Oxides, Cell Death/radiation effects, Twist-Related Protein 1/genetics, Acetylcysteine, 3. Good health, Gene Knockdown Techniques, RNA, Irradiation, Non-Small-Cell Lung/pathology, Reactive oxygen species, Reactive Oxygen Species |
| Popis: | TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells. |
| Druh dokumentu: | Article |
| Popis souboru: | 490~495 |
| Jazyk: | English |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.05.030 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/24845567 https://europepmc.org/article/MED/24845567 http://www.osti.gov/scitech/biblio/22416612 https://pubmed.ncbi.nlm.nih.gov/24845567/ https://ir.ymlib.yonsei.ac.kr/handle/22282913/99272 http://www.sciencedirect.com/science/article/pii/S0006291X14008845 https://www.sciencedirect.com/science/article/pii/S0006291X14008845 |
| Rights: | Elsevier TDM CC BY NC ND |
| Přístupové číslo: | edsair.doi.dedup.....118d919af5a21d0ccafe2bc7f637d963 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells. |
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| ISSN: | 0006291X |
| DOI: | 10.1016/j.bbrc.2014.05.030 |