title: Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines.
abstract: Apigenin, a common dietary flavonoid, has been shown to induce cell cycle arrest in both epidermal and fibroblast cells and inhibit skin tumorigenesis in murine models. The present study assessed the influence of apigenin on cell growth and the cell cycle in the human colon carcinoma cell lines SW480, HT-29, and Caco-2. Treatment of each cell line with apigenin (0-80 microM) resulted in a dose-dependent reduction in both cell number and cellular protein content, compared with untreated control cultures. DNA flow cytometric analysis indicated that treatment with apigenin resulted in G2/M arrest in all three cell lines in a time- and dose-dependent manner. Apigenin treatment (80 microM) for 48 h produced maximum G2/M arrest of 64%, 42%, and 26% in SW480 cells, HT-29 cells, and Caco-2 cells, respectively, in comparison with control cells (15%). The proportion of S-phase cells was not altered by apigenin treatment in each of the three cell lines. The G2/M arrest was reversible after 48 h of apigenin treatment in the most sensitive cell line SW480. The degree of G2/M arrest by apigenin was inversely correlated with the corresponding inhibition of cell growth measurements in all three cell lines (r = -0.626 to -0.917, P</=0. 005). Moreover, an immune complex kinase assay demonstrated an inhibition of p34(cdc2) kinase activity, a critical enzyme in G2/M transition, in each cell line after treatment with apigenin (50-80 microM). Western blot analyses indicated that both p34(cdc2) and cyclin B1 proteins were also decreased after apigenin treatment. These results indicate that apigenin inhibits colon carcinoma cell growth by inducing a reversible G2/M arrest and that this arrest is associated, at least in part, with inhibited activity of p34(cdc2) kinase and reduced accumulation of p34(cdc2) and cyclin B1 proteins. Differences in induction of G2/M arrest by apigenin in the three colon carcinoma cell lines suggest that dietary apigenin may be differentially effective against tumors with specific mutational spectra. Mol. Carcinog. 28:102-110, 2000.
authors.affiliation: Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa 50011-1061, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Heideman
authors.forename: C S
authors.initials: CS
authors.lastname: Chung
authors.forename: J C
authors.initials: JC
authors.lastname: Pelling
authors.forename: K J
authors.initials: KJ
authors.lastname: Koehler
authors.forename: D F
authors.initials: DF
authors.lastname: Birt
mesh_terms: D047310:Apigenin; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D005419:Flavonoids / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D005419:Flavonoids; D047310:Apigenin; D016203:CDC2 Protein Kinase