HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Gastrointest Liver Physiol 292: G66-G75, 2007. First published August 10, 2006; doi:10.1152/ajpgi.00248.2006
0193-1857/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/1/G66    most recent 00248.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lim, D. Y. Articles by Park, J. H. Y. Search for Related Content PubMed PubMed Citation Articles by Lim, D. Y. Articles by Park, J. H. Y.

HORMONES AND SIGNALING

Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin

¹Department of Food Science and Nutrition, Hallym University, Chuncheon; ²Department of Food Science and Nutrition, Dankook University, Seoul, Korea; and ³Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, Illinois

Submitted 6 June 2006 ; accepted in final form 2 August 2006

Luteolin is 3',4',5,7-tetrahydroxyflavone found in celery, green pepper, and perilla leaf that inhibits tumorigenesis in animal models. We examined luteolin-mediated regulation of cell cycle progression and apoptosis in the HT-29 human colon cancer cell line. Luteolin decreased DNA synthesis and viable HT-29 cell numbers in a concentration-dependent manner. It inhibited cyclin-dependent kinase (CDK)4 and CDK2 activity, resulting in G₁ arrest with a concomitant decrease of phosphorylation of retinoblastoma protein. Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P < 0.05) observed in cells treated with 40 µmol/l luteolin. Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D₁ levels decreased after luteolin treatment, although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G₂/M arrest at 24 h posttreatment by downregulating cyclin B₁ expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspases 3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21^CIP1/WAF1, survivin, Mcl-1, Bcl-x_L, and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells. We demonstrate that luteolin promotes both cell cycle arrest and apoptosis in the HT-29 colon cancer cell line, providing insight about the mechanisms underlying its antitumorigenic activities.

cyclin-dependent kinase; cyclin; G₁ phase arrest; G₂/M phase arrest; cell division cycle 2