Journal
CANCER PREVENTION RESEARCH
Volume 7, Issue 4, Pages 466-474Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-13-0387
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Funding
- Hormel Foundation
- NIH [CA027502, CA120388, R37 CA081064]
- NIESH [ES016548]
- National Leap Research Program through the National Research Foundation [2010-0029233]
- Global Frontier Project grant of National Research Foundation [NRF-M1AXA002-2012M3A6A4054949]
- Ministry of Education, Science and Technology of Korea
- WCU (World Class University) through the National Research Foundation of Korea [R31-10056]
- Ministry of Education, Science and Technology
- National Research Foundation of Korea [2012M3A6A4054949, 2010-0029233] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 G(1) 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. (c) 2014 AACR.
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