Abstract
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
INK4A
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
INK4A
-dependent cell cycle checkpoint signalling pathway orchestrated by UHRF1 and DNMT1 down-regulation.