Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation

被引：57

作者：

Krifa, Mounira ^{[1
,2
]}

Alhosin, Mahmoud ^{[1
]}

Muller, Christian D. ^{[3
]}

Gies, Jean-Pierre ^{[1
]}

Chekir-Ghedira, Leila ^{[2
]}

Ghedira, Kamel ^{[2
]}

Mely, Yves ^{[1
]}

Bronner, Christian ^{[4
]}

Mousli, Marc ^{[1
]}

机构：

[1] Univ Strasbourg, Fac Pharm, Lab Biophoton & Pharmacol, UMR CNRS 7213, F-67401 Illkirch Graffenstaden, France

[2] Fac Pharm Monastir, Unite Pharmacognosie Biol Mol UR 07 03 99, Monastir, Tunisia

[3] Univ Strasbourg, Fac Pharm, Lab Innovat Therapeut, UMR CNRS 7200, F-67401 Illkirch Graffenstaden, France

[4] CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2013年 / 32卷

关键词：

Apoptosis; Epigenetic modifications; Gall extract; Tumor suppressor genes; UHRF1; TUMOR-SUPPRESSOR GENES; DNA METHYLATION; SRA DOMAIN; IN-VITRO; INDUCTION; ARREST; (-)-EPIGALLOCATECHIN-3-GALLATE; PROLIFERATION; INHIBITORS; EXPRESSION;

D O I：

10.1186/1756-9966-32-30

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：10

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