Glycyrrhizic acid has been shown to possess anti-inflammation, antiviral and chemoprotective activity against tumors. We evaluated the protective effects of glycyrrhizic acid in UVB-radiation-induced skin tumor formation in SKH-1 hairless mice and the early molecular biomarkers of these effects. Mice irradiated at 180 mJ/cm2 twice per week showed 100% tumor incidence in 20 weeks. Feeding with glycyrrhizic acid prior to UVB irradiation caused delays in tumor appearance, multiplicity and size. Feeding with glycyrrhizic acid for 2 weeks before a single UVB irradiation (180 mJ/cm2) resulted in significant decrease in UVB-radiation-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and apoptotic sunburn cells together with an increase in p53- and p21/Cip1-positive cell populations in epidermis. Simultaneously, glycyrrhizic acid also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. Thus glycyrrhizic acid ameliorates UVB-radiation-induced tumorigenesis via downregulation of cell proliferation controls involving thymine dimer, PCNA, apoptosis and transcription factor NF-κB and of inflammatory responses involving COX-2, PGE2 and NO while upregulating of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.
Molecular Mechanisms Underlying Chemopreventive Activities of Glycyrrhizic Acid against UVB-Radiation-Induced Carcinogenesis in SKH-1 Hairless Mouse Epidermis
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Jaw-Ming Cherng, Kuen-Daw Tsai, Yu-Whay Yu, Jung-Chung Lin; Molecular Mechanisms Underlying Chemopreventive Activities of Glycyrrhizic Acid against UVB-Radiation-Induced Carcinogenesis in SKH-1 Hairless Mouse Epidermis. Radiat Res 1 August 2011; 176 (2): 177–186. doi: https://doi.org/10.1667/RR2510.1
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