Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells |
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| Affiliation: | 1. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;2. Sub-Department of Toxicology, Wageningen University, Wageningen, The Netherlands;3. Biometris, Wageningen University, Wageningen, The Netherlands;4. RIKILT Wageningen UR, Wageningen, The Netherlands;1. Department of Obstetrics and Gynecology, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Republic of Korea;2. Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea;1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, Mumbai, Maharashtra, India;2. SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, Maharashtra, India;3. Birla Institute of Technology and Science, Pilani, Rajasthan, India;1. School of Stomatology, Lanzhou University, Lanzhou 730000, Gansu, China;2. Institute of Biomechanics and Medical Engineering, Lanzhou University, Lanzhou 730000, Gansu, China;3. Department of Stomatology, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China;1. Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan;2. Nichimo Biotics Co., Ltd., Tokyo, 140-0002, Japan;1. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;2. Curso de Farmácia, Universidade Federal do Rio de Janeiro, Macaé, RJ, Brazil;3. Programa de Pós-Graduação em Ciências da Saúde, Laboratório de Nanotecnologia, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil;4. Programa de Pós-Graduação em Ciências Fisiológicas, Laboratório de Histologia, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil;5. Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil |
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| Abstract: | Daidzein, which belongs to the group of isoflavones from soybeans, has been extensively researched prostate, cervix, brain, breast, and colon cancer cell lines. However, daidzein has not been thoroughly investigated in human hepatic cancer cells; therefore, we investigated whether it inhibits hepatic cancer cell growth. Decreased cell proliferation was measured in daidzein-treated hepatic cancer cells (SK-HEP-1) upon real-time cell electronic sensing analysis however, it was not affected on normal human hepatocytes (Chang). Daidzein-induced apoptosis was demonstrated by comet and TUNEL assay. Moreover, we conducted two-dimensional electrophoresis to study the mechanism of daidzein-induced apoptosis in daidzein-treated SK-HEP-1 cells. Expression of peroxiredoxin-3 (Prdx-3), which modulates redox homeostasis of cells, was increased in protein analysis. Additionally, we measured the levels of reactive oxygen species and it was decreased in daidzein-treated SKHEP-1 cells. Daidzein-induced apoptosis in SK-HEP-1 cells was also associated with the up-regulation of Bak and down-regulation of Bcl-2 and Bcl-xL proteins. Moreover, daidzein treatment increased in the release of mitochondrial cytochrome c and activation of APAF-1, caspase 9 and caspase 3. Overall, these result indicate that daidzein is a potent inducer of apoptosis in hepatic cancer cells via mitochondrial pathway. |
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| Keywords: | Liver cancer Apoptosis Daidzein Proxiredoxin 3 |
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