Ming-Ju Hsieh1, Mu-Kuan Chen2, Chih-Jung Chen3, Ming-Chang Hsieh4, Yu-Sheng Lo5, Yi-Ching Chuang5, Hui-Ling Chiou6, Shun-Fa Yang7. 1. Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan; School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan. 2. Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan. 3. Department of Surgical Pathology, Changhua Christian Hospital, Changhua 500, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; School of Medicine, Chung Shan Medical University, Taichuang 40201, Taiwan. 4. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. 5. Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan. 6. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: hlchiou@csmu.edu.tw. 7. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: ysf@csmu.edu.tw.
Abstract
BACKGROUND: Extensive research results support the use of herbal medicine or natural food to augment therapy for various cancers. Studies have associated glabridin with numerous biological activities, such as regulating energy metabolism and estrogenic, neuroprotective, antiosteoporotic, and skin-whitening activities. HYPOTHESIS/ PURPOSE: However, how glabridin affects tumor cell autophagy has not been clearly determined. METHODS: Autophagy is a lysosomal degradation pathway essential for cell survival and tissue homeostasis. In this study, the roles of autophagy and related signaling pathways during glabridin-induced autophagy in human liver cancer cells were investigated. Additionally, the molecular mechanism of the anticancer effects of glabridin in human hepatoma cells was investigated. RESULTS: The results revealed that glabridin significantly inhibited cell proliferation in human hepatoma cells. Glabridin induced apoptosis dose-dependently in Huh7 cells through caspase-3, -8, and -9 activation and PARP cleavage. Furthermore, autophagy was detected as early as 12h after exposure to a low dose of glabridin, as indicated by the up-regulated expression of LC3-II and beclin-1 proteins. The inhibition of JNK1/2 and p38 MAPK by specific inhibitors significantly reduced glabridin-induced activation of caspases-3, -8, and -9. Blocking autophagy sensitize the Huh7 cells to apoptosis. CONCLUSION: This study demonstrated for the first time that autophagy occurs earlier than apoptosis does during glabridin-induced apoptosis in human liver cancer cell lines. Glabridin induces Huh7 cell death through apoptosis through the p38 MAPK and JNK1/2 pathways and is a potential chemopreventive agent against human hepatoma.
BACKGROUND: Extensive research results support the use of herbal medicine or natural food to augment therapy for various cancers. Studies have associated glabridin with numerous biological activities, such as regulating energy metabolism and estrogenic, neuroprotective, antiosteoporotic, and skin-whitening activities. HYPOTHESIS/ PURPOSE: However, how glabridin affects tumor cell autophagy has not been clearly determined. METHODS: Autophagy is a lysosomal degradation pathway essential for cell survival and tissue homeostasis. In this study, the roles of autophagy and related signaling pathways during glabridin-induced autophagy in humanliver cancer cells were investigated. Additionally, the molecular mechanism of the anticancer effects of glabridin in humanhepatoma cells was investigated. RESULTS: The results revealed that glabridin significantly inhibited cell proliferation in humanhepatoma cells. Glabridin induced apoptosis dose-dependently in Huh7 cells through caspase-3, -8, and -9 activation and PARP cleavage. Furthermore, autophagy was detected as early as 12h after exposure to a low dose of glabridin, as indicated by the up-regulated expression of LC3-II and beclin-1 proteins. The inhibition of JNK1/2 and p38 MAPK by specific inhibitors significantly reduced glabridin-induced activation of caspases-3, -8, and -9. Blocking autophagy sensitize the Huh7 cells to apoptosis. CONCLUSION: This study demonstrated for the first time that autophagy occurs earlier than apoptosis does during glabridin-induced apoptosis in humanliver cancer cell lines. Glabridin induces Huh7 cell death through apoptosis through the p38 MAPK and JNK1/2 pathways and is a potential chemopreventive agent against humanhepatoma.
Authors: Monica Benvenuto; Loredana Albonici; Chiara Focaccetti; Sara Ciuffa; Sara Fazi; Loredana Cifaldi; Martino Tony Miele; Fernando De Maio; Ilaria Tresoldi; Vittorio Manzari; Andrea Modesti; Laura Masuelli; Roberto Bei Journal: Int J Mol Sci Date: 2020-09-10 Impact factor: 5.923
Authors: Giulia Pastorino; Laura Cornara; Sónia Soares; Francisca Rodrigues; M Beatriz P P Oliveira Journal: Phytother Res Date: 2018-08-17 Impact factor: 5.878