Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer Ca Ski cells.

Abstract

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.

• Authors: Fabienne Hirchaud, François Hermetet, Mourboul Ablise, Sylvie Fauconnet, Dominique A Vuitton, Jean-Luc Prétet, Christiane Mougin
• Journal: Planta medica (Planta Med) Vol. 79 Issue 17 Pg. 1628-35 (Nov 2013) ISSN: 1439-0221 [Electronic] Germany
• PMID: 24214831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Antineoplastic Agents, Phytogenic
• BH3 Interacting Domain Death Agonist Protein
• Bid protein, rat
• Caspase Inhibitors
• Chalcones
• Drugs, Chinese Herbal
• E6 protein, Human papillomavirus type 16
• Oncogene Proteins, Viral
• Proto-Oncogene Proteins c-bcl-2
• Repressor Proteins
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Cytochromes c
• isoliquiritigenin
• Caspases

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Caspase Inhibitors (pharmacology, therapeutic use)
• Caspases (metabolism)
• Cell Line, Tumor
• Chalcones (pharmacology, therapeutic use)
• Cytochromes c (metabolism)
• Down-Regulation
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Female
• Glycyrrhiza (chemistry)
• HeLa Cells
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects)
• Oncogene Proteins, Viral (metabolism)
• Phytotherapy
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Repressor Proteins (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• Uterine Cervical Neoplasms (drug therapy, metabolism)
• bcl-2-Associated X Protein (metabolism)