Isoliquiritigenin Induces Caspase-Dependent Apoptosis via Downregulation of HPV16 E6 Expression in Cervical Cancer Ca Ski Cells.

Autor: Hirchaud, Fabienne, Hermetet, François, Ablise, Mourboul, Fauconnet, Sylvie, Vuitton, Dominique A., Prétet, Jean-Luc, Mougin, Christiane
Předmět:
Zdroj: Planta Medica; Nov2013, Vol. 79 Issue 17, p1628-1635, 8p
Abstrakt: Flavonoids have antitumoral properties and may be attractive candidates as anticancer therapy. Isoliquiritigenin which is a constituent of licorice (Glycyrrhiza inflata), a plant commonly used in traditional Uyghur medicine in Xinjiang, China, was studied for antiproliferative and apoptotic activity in human cervical cancer cells, Ca Ski, SiHa, HeLa, and C-33A. Its molecular mechanism of action was specifically examined in Ca Ski cells. Isoliquiritigenin decreased cell viability, induced cell accumulation in G2/M and morphological and biochemical features of apoptosis in the four cancer cell lines. In Ca Ski cells, isoliquiritigenin led to a downregulation of HPV16 E6 expression associated with an increase of p53 and p21 levels, enhanced expression of Bax and decreased expression of Bcl-2 and Bid proform triggering dissipation of the mitochondrial membrane potential, released cytochrome c to the cytosol followed by activation of caspase cascadewith cleavage of caspase-9, caspase-3, and PARP. Caspase-8 was also cleaved. Moreover treatment with a pan-caspase inhibitor prevented apoptosis. As Ca Ski cells are representative of carcinoma naturally occurring in the cervix, our results suggest a potential benefit of isoliquiritigenin for cervical cancer prevention and treatment. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index