title: Curcumin suppresses proliferation of colon cancer cells by targeting CDK2.
abstract: Curcumin, the yellow pigment of turmeric found in Southeast Indian food, is one of the most popular phytochemicals for cancer prevention. Numerous reports have demonstrated modulation of multiple cellular signaling pathways by curcumin and its molecular targets in various cancer cell lines. To identify a new molecular target of curcumin, we used shape screening and reverse docking to screen the Protein Data Bank against curcumin. Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Furthermore, curcumin induced G1 cell-cycle arrest, which is regulated by CDK2 in HCT116 cells. Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of retinoblastoma (Rb), a well-known CDK2 substrate, was reduced by curcumin. Because curcumin induced cell-cycle arrest, we investigated the antiproliferative effect of curcumin on HCT116 colon cancer cells. In this experiment, curcumin suppressed HCT116 cell proliferation effectively. To determine whether CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. As expected, HCT116 sh-CDK2 cells exhibited G1 arrest and reduced proliferation. Because of the low levels of CDK2 in HCT116 sh-CDK2 cells, the effects of curcumin on G1 arrest and cell proliferation were not substantially relative to HCT116 sh-control cells. From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells.
authors.affiliation: University of Minnesota, 801 16th Avenue NE, Austin, MN 55912. Phone: 507-437-9600; Fax: 507-437-9606; zgdong@hi.umn.edu; and Ki Won Lee, Seoul National University, Seoul, Republic of Korea. kiwon@snu.ac.kr.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Lim
authors.forename: Sung-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Zunnan
authors.initials: Z
authors.lastname: Huang
authors.forename: Do Young
authors.initials: DY
authors.lastname: Lim
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008958:Models, Molecular; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D003474:Curcumin