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Acetylbritannilactone suppresses growth via upregulating KLF4 expression in HT29 colorectal cancer cells
Author(s) -
Fang Xin mei,
Liu Bin,
Liu Ya bin,
Wang Jun jie,
Li Bing hui
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.641.10
Acetylbritannilactone (ABL) is a new active compound isolated from Inula Britannica L, a traditional Chinese medicinal herb. It has been reported that ABL can inhibit the proliferation of vessel smooth muscle cells (VSMCs) and neointima formation after balloon injury in rats. ABL also shows chemo‐preventive properties by inducing cell apoptosis in breast and ovarian cancers, but the antitumor activity and the molecular targets of ABL in colon cancer cells have not been determined. In this study, we showed that ABL inhibits the growth in dose‐ and time‐dependent manners by inducing cell cycle arrest in G0/G1 phase of HT29 human colon cancer cells. This suppression was accompanied by a strong decrease of cyclin E and CDK4 protein level, and an increase in p21 protein expression in HT29 cells. We also show that ABL‐induced growth inhibition is associated the up‐regulation of KLF4 expression. The overexpression of KLF4 by infection of pAd‐KLF4 resulted in the growth inhibition, with decrease in the protein level of cyclin E and CDK4, and increase in the expression of p21, which was the similar effect as ABL. Conversely, knockdown of KLF4 using specific siRNA impaired the ABL‐induced growth inhibition in HT29 cells. These results suggest that KLF4 as an important cellular target of ABL mediates the growth inhibition of HT‐29 cells induced by ABL via up‐regulating p21 expression.