Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice.
Glycyrrhetinic acid is an aglycone of glycyrrhizic acid, another major active component of licorice roots. Licorice root extract has been used for a long time as a medicine and a natural sweetening additive. In the present study, we found that glycyrrhetinic acid inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA) mediated oxidative stress and tumor promotion in murine skin. Topical application of TPA alone in mouse skin enhances ornithine decarboxylase activity and also increases [3H]-thymidine incorporation in DNA. Topical application of TPA also resulted in the depletion of glutathione, activities of glutathione metabolizing and antioxidant enzymes. Application of glycyrrhetinic acid prior to TPA treatment reduces this enhanced ODC activity, [3H]-thymidine incorporation in DNA and oxidative stress. Glycyrrhetinic acid was also found to inhibit DMBA/TPA-induced skin tumor formation at doses of 1.25 and 2.5 mg by reducing the number of tumors per mouse by 24% (P < 0.05) and 62% (P < 0.05), respectively. These results suggest that glycyrrhetinic acid, an antioxidant, is a potential chemopreventive agent that can inhibit DMBA/TPA-induced cutaneous oxidative stress and tumor promotion.
Agarwal
Mukesh Kumar
MK
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard University, New Delhi, India.
Iqbal
Mohammad
M
Athar
Mohammad
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002273:Carcinogens; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006035:Glycyrrhiza; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010936:Plant Extracts; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D016166:Free Radical Scavengers; D010936:Plant Extracts; D013755:Tetradecanoylphorbol Acetate; D006034:Glycyrrhetinic Acid