Isoliquiritigenin Induces Caspase-Dependent Apoptosis via Downregulation of HPV16 E6 Expression in Cervical Cancer Ca Ski Cells
2013
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
cascade with 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.
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