Acetylbritannilactone suppresses growth via upregulation of kr�ppel-like transcription factor 4 expression in HT-29 colorectal cancer cells

Abstract

Abstract. 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 vascular smooth muscle cells (VSMCs) and neointima formation after balloon injury in rats. ABL also shows chemopreventive 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 HT-29 human colon cancer cells. This suppression was accompanied by a strong decrease of cyclin E and CDK4 protein levels, and an increase in p21 protein expression in HT-29 cells. We also show that ABL-induced growth inhibition is associated with the upregulation of KLF4 expression. The overexpression of KLF4 by infection with pAd-KLF4 resulted in growth inhibition, with decrease in the protein levels of cyclin E and CDK4, and increase in the expression of p21, similarly to the effects of ABL. Conversely, knockdown of KLF4 using a specific siRNA impaired the ABL-induced growth inhibition in HT-29 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 upregulation of p21 expression.

Inula L. Secondary Metabolites against Oxidative Stress-Related Human Diseases

“…1- O -acetylbritannilactone ( 12 ) (Figure 2) is a 1,10- seco -eudesmanolide sesquiterpene that, like compound 11 , has an α-methylene–γ-lactone skeleton, found in Inula britannica var. chinensis and Inula japonica [12], and that possesses cytotoxic potential [58,59] and anti-inflammatory properties [60,61]. A recent study by Wei et al [62], found that the 6-deoxy1- O -acetylbritannilactone with a methylene at C-14 position, an analogue of 1- O -acetylbritannilactone ( 12 ) labelled as 1- O -acetyl-4α H -1,10- seco -eudesma-5(6),10(14),11(13)-trien-12,8β-olide ( 13 ) (Figure 2), exhibits an anti-inflammatory effect.…”

Phytochemical profiling, antioxidant and antiproliferation potential of Euphorbia milii var.: Experimental analysis and in-silico validation

“…Tin et al ( Matsuda, 2008 ) reported that artemisinin inhibited the proliferation of breast cancer cells via selectively downregulating the levels of the CDK2 and CDK4, cyclin E, cyclin D1 and the E2F1 transcription factor. Fang et al (2011) reported that acetylbritannilactone inhibited the growth of HT-29 human colon cancer cells by inducing cell cycle arrest in G0/G1 phase and this suppression was accompanied by a marked decrease of cyclin E and CDK4 protein levels. In present study, we propose that the cytotoxic effect of E. milii on invasive growth of HepG2 cells were associated with protein levels of CDK2 and E2F1 involved in CDK2/Rb/E2F signaling.…”

Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells

“…1-O-acetylbritannilactone (ABL), a compound extracted from Inula britannica L., has been studied as a preventative agent against cancer and inflammatory diseases [ 8 – 11 ]. Previous reports showed that ABL treatment inhibited PDGF-induced vascular smooth muscle cell (VSMC) proliferation and migration, which are key steps in the progression of atherosclerosis and restenosis [ 10 ].…”