title: Tetrahydrocurcumin induces G2/M cell cycle arrest and apoptosis involving p38 MAPK activation in human breast cancer cells.
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.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Zhe-Nan
authors.initials: ZN
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Yuan-Hao
authors.initials: YH
authors.lastname: Lv
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Fan
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: fengqiu20070118@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: gaoxiumei@tjutcm.edu.cn.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C096277:tetrahydrocurcumin; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Apoptosis; Breast cancer; Curcumin; G2/M cell cycle arrest; Tetrahydrocurcumin; p38 MAPK