title: Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro.
abstract: Curcumin, the major pigment of the dietary spice turmeric, has the potential for chemoprevention by promotion of apoptosis. Here, we investigated the molecular mechanisms of curcumin in glycolytic inhibition and apoptotic induction in human colorectal cancer HCT116 and HT29 cells. On the one hand, curcumin downregulated the expression and activity of hexokinase II (HKII) in HCT116 and HT29 cells in a concentration-dependent manner, but had little effect on the other key glycolytic enzymes (PFK, PGM, and LDH). On the other, curcumin induced dissociation of HKII from the mitochondria, resulting in mitochondrial-mediated apoptosis. Furthermore, the phosphorylation of mitochondrial HKII through AKT was responsible for the curcumin-induced dissociation of HKII, which was different from the mechanism of HKII inhibitor 3-BrPA. These results have important implications for the metabolism reprogramming effect and the susceptibility to curcumin-induced mitochondrial cytotoxicity through the regulation of HKII, and provide a molecular basis for the development of naturally compounds as novel anticancer agents for colorectal carcinoma.
authors.affiliation: aJiangsu Institute of Cancer Research bJiangsu Research Institute of Geriatrics, Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Fan
authors.forename: Qingsen
authors.initials: Q
authors.lastname: Chen
authors.forename: Guojian
authors.initials: G
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D045325:HCT116 Cells; D019073:HT29 Cells; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006593:Hexokinase; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin