Indole-3-carbinol activates the cyclin-dependent kinase inhibitor p15(INK4b) gene.
Indole-3-carbinol (I3C) is a naturally occurring compound found in vegetables such as broccoli and cauliflower, and has been shown to arrest human tumor cells in the G1 phase of the cell cycle. However, the molecular mechanism responsible for this effect has not been sufficiently elucidated. We report here that I3C activates the cyclin-dependent kinase (CDK) inhibitor p15INK4b gene through its promoter, accompanied by cell growth inhibition in HaCaT cells. Treatment with I3C almost did not affect the expressions of the other CDK inhibitors such as p19INK4d, p21WAF1 and p27Kip1. These results suggest that p15INK4b is an important molecular target of I3C among CDK inhibitors.
Matsuzaki
Youichirou
Y
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Koyama
Makoto
M
Hitomi
Toshiaki
T
Kawanaka
Mayumi
M
Sakai
Toshiyuki
T
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism; D007700:Kinetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism*
D016588:Anticarcinogenic Agents; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D007211:Indoles; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C016517:indole-3-carbinol; D018844:Cyclin-Dependent Kinases