title: Molecular mechanisms underlying chemopreventive activities of glycyrrhizic acid against UVB-radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Chung Shan Medical University Hospital and Chung Shan Medical University, 110 Jianguo N. Road, Sec. 1, Taichung, Taiwan.
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
authors.forename: Kuen-Daw
authors.initials: KD
authors.lastname: Tsai
authors.forename: Yu-Whay
authors.initials: YW
authors.lastname: Yu
authors.forename: Jung-Chung
authors.initials: JC
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004249:DNA Damage; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D016328:NF-kappa B / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013471:Sunburn / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D019695:Glycyrrhizic Acid; D051546:Cyclooxygenase 2