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

Journal of Experimental & Clinical Cancer Research

Marc Mousli³  Christian Bronner¹  Yves Mély³  Kamel Ghedira⁴  Leila Chekir-Ghedira⁴  Jean-Pierre Gies³  Christian D Muller²  Mahmoud Alhosin³  Mounira Krifa⁴ 

[1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM, Parc d’innovation, 1 rue Laurent Fries, Illkirch, Cedex 67404, France;UMR CNRS 7200, Laboratoire d’Innovation Thérapeutique, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France;UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, CS 60024, Illkirch, Cedex F-67401, France;Unité de Pharmacognosie/Biologie Moléculaire 99/UR/07-03. Faculté de Pharmacie de Monastir, Rue Avicenne 5000, Monastir, Tunisie

关键词: UHRF1;    Tumor suppressor genes;    Gall extract;    Epigenetic modifications;    Apoptosis;   

Others  :  825081
DOI  :  10.1186/1756-9966-32-30

 received in 2013-03-18, accepted in 2013-05-17,  发布年份 2013

【 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.

【 授权许可】

   
2013 Krifa et al.; licensee BioMed Central Ltd.

【 图 表 】

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