Tetrahydrocurcumin induces G2/M cell cycle arrest and apoptosis involving p38 MAPK activation in human breast cancer cells |
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| Affiliation: | 1. Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China;2. Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing, China;1. School of Pharmacy, College of Medicine, China Medical University, Taichung, Taiwan;2. The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medicine, China Medical University, Taichung, Taiwan;3. Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan;4. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan;5. Department of Food Science, Rutgers University, New Brunswick, NJ, USA;6. Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan;7. Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan;8. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan |
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| Abstract: | Curcumin (CUR) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. In recent years, it has been reported that CUR exhibits significant anti-tumor activity in vivo. However, the pharmacokinetic features of CUR have indicated poor oral bioavailability, which may be related to its extensive metabolism. The CUR metabolites might be responsible for the antitumor pharmacological effects in vivo. Tetrahydrocurcumin (THC) is one of the major metabolites of CUR. In the present study, we examined the efficacy and associated mechanism of action of THC in human breast cancer MCF-7 cells for the first time. Here, THC exhibited significant cell growth inhibition by inducing MCF-7 cells to undergo mitochondrial apoptosis and G2/M arrest. Moreover, co-treatment of MCF-7 cells with THC and p38 MAPK inhibitor, SB203580, effectively reversed the dissipation in mitochondrial membrane potential (Δψm), and blocked THC-mediated Bax up-regulation, Bcl-2 down-regulation, caspase-3 activation as well as p21 up-regulation, suggesting p38 MAPK might mediate THC-induced apoptosis and G2/M arrest. Taken together, these results indicate THC might be an active antitumor form of CUR in vivo, and it might be selected as a potentially effective agent for treatment of human breast cancer. |
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| Keywords: | Curcumin Tetrahydrocurcumin Apoptosis G2/M cell cycle arrest p38 MAPK Breast cancer |
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