Myung Woul Han1, Jong Cheol Lee, Jun-Young Choi, Gui Chul Kim, Hyo Won Chang, Hae Yun Nam, Seong Who Kim, Sang Yoon Kim. 1. Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olymhic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea. sykim2@amc.seoul.kr and Seong Who Kim, MD, Ph.D., Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine Seoul, Republic of Korea. E-mail: swhokim@amc.seoul.kr.
Abstract
BACKGROUND/AIM: Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance. MATERIALS AND METHODS: TAK1 phosphorylation in MDA-MB231 breast cancer cells was evaluated by western blotting. The regulatory effects of the TAK1 inhibitor and autophagy inhibitor were assessed by cell morphology, cell survival and induction of apoptosis. RESULTS: Radiation induced the phosphorylation of TAK1, whereas the inhibition of TAK1 activity enhanced the cytotoxicity of radiation in MDA-MB231 cells. Autophagy inhibitors significantly enhanced radiation-induced apoptosis of MDA-MB231 cells. This augmentation in radiosensitivity seemed to result from the suppression of TAK1 activation. CONCLUSION: Inhibition of autophagy enhanced radiosensitivity through suppression of radiation-induced TAK1 activation, suggesting that the modulation of TAK1-induced autophagy may be a good therapeutic strategy to treat radioresistant breast cancer.
BACKGROUND/AIM: Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance. MATERIALS AND METHODS:TAK1 phosphorylation in MDA-MB231 breast cancer cells was evaluated by western blotting. The regulatory effects of the TAK1 inhibitor and autophagy inhibitor were assessed by cell morphology, cell survival and induction of apoptosis. RESULTS: Radiation induced the phosphorylation of TAK1, whereas the inhibition of TAK1 activity enhanced the cytotoxicity of radiation in MDA-MB231 cells. Autophagy inhibitors significantly enhanced radiation-induced apoptosis of MDA-MB231 cells. This augmentation in radiosensitivity seemed to result from the suppression of TAK1 activation. CONCLUSION: Inhibition of autophagy enhanced radiosensitivity through suppression of radiation-induced TAK1 activation, suggesting that the modulation of TAK1-induced autophagy may be a good therapeutic strategy to treat radioresistant breast cancer.
Entities:
Keywords:
Autophagy; TAK1; breast cancer; radioresistance