Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16§ssup§INK4A§esup§ re-expression related to UHRF1 and DNMT1 down-regulation

Several reports have described the potential effects of natural compounds as anti-cancer agents in vitro as well as in vivo. the aim of this study was to evaluate the anti-cancer effect of limoniastrum guyonianum aqueous gall extract (g extract) and luteolin in the human cervical cancer hela cell line,and,if so,to clarify the underlying mechanism. our results show that g extract and luteolin inhibited cell proliferation and induced g2/m cell cycle arrest in a concentration and time-dependent manner. both natural products induced programmed cell death as confirmed by the presence of hypodiploid g0/g1 cells. these effects are associated with an up-regulation of the expression of the tumor suppressor gene p16 §ssup§ ink4a §esup§ and a down-regulation of the expression of the anti-apoptotic actor uhrf1 and its main partner dnmt1. moreover,g extract- and luteolin-induced uhrf1 and dnmt1 down-regulation is accompanied with a global dna hypomethylation in hela cell line. altogether our results show that g extract mediates its growth inhibitory effects on human cervical cancer hela cell line likely via the activation of a p16§ssup§ink4a§esup§ -dependent cell cycle checkpoint signalling pathway orchestrated by uhrf1 and dnmt1 down-regulation. © 2013 krifa et al.; licensee biomed central ltd.