Topical application of Gallic acid suppresses the 7,12-DMBA/Croton oil induced two-step skin carcinogenesis by modulating anti-oxidants and MMP-2/MMP-9 in Swiss albino mice.
Gallic acid (GA - 3,4,5-trihydroxybenzoic acid), a dietary anti-oxidant has been shown to inhibit cancer cell growth in in vitro. Herein, we investigated the in vivo chemo preventive activity of GA on 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil induced two-step skin carcinogenesis in Swiss albino mice. Skin tumor incidence and tumor volume were recorded during the 16 weeks of experimental period. In addition, LDH-isozyme shift, skin collagen content, activities of matrix metalloproteinases (MMP-2/MMP-9) enzymes and enzymatic and non-enzymatic antioxidant were studied in the skin and serum of experimental mice. Tumor incidence was significantly increased in the DMBA/Croton oil induced mice (100%; p<0.001) when compared to GA co-treated mice (60%; p<0.01) and 5-FU treated mice (50%; p<0.01). Skin collagen content, MMPs activities, LDH-isoenzymes and MMP-2/-9 expressions were increased in DMBA/Croton oil induced skin while decreased levels of enzymatic (GST, SOD, CAT & GPx) and non-enzymatic anti-oxidant (GSH) were noticed. On the other hand, GA co-treatment exhibited a significant protection by reverting back the altered levels of LDH-isoenzymes, antioxidants, collagen and MMP-2/MMP-9 activities. The results of this study indicate that topical application of GA inhibits DMBA/Croton oil induced two-stage skin carcinogenic process by modulating the antioxidants and MMPs (-2 & -9) in the mouse skin.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India.
Vimala
V
Subramanian
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India.
Balaji
B
Venkatesan
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India.
Anusha
A
Tumala
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India. Electronic address: vellaie@gmail.com.
Elangovan
E
Vellaichamy
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D003436:Croton Oil / Q000633:toxicity*; D005707:Gallic Acid / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control
D000975:Antioxidants; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D005707:Gallic Acid; D003436:Croton Oil; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Anticancer activity; DMBA/Croton oil; GST; Gallic acid; MMP; Skin cancer