title: Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis.
abstract: The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects. Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However, in mice pretreated with 30 microL eugenol, no tumors were detected until 8 wk (following anti-initiation protocol) and until 14 wk (following antipromotion protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively. The effect of eugenol was assessed on specific stages of carcinogenesis. Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA. However, pretreatment with eugenol led to overexpression of these genes, which probably helped stimulate apoptosis of the initiated cells. To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol, its effect was investigated on markers of tumor promotion and inflammation: ODC activity and iNOS and COX-2 expression, and on levels of proinflammatory cytokines (IL-6, TNF-alpha, and PGE(2)). Eugenol markedly inhibited all. Eugenol also inhibited the upstream signaling molecule: NF-kappaB, which regulates the expression of these genes. TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol. From these results, it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative, anti-inflammatory, and antioxidant activities.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard, New Delhi, India.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Kaur
authors.forename: Mohammad
authors.initials: M
authors.lastname: Athar
authors.forename: M Sarwar
authors.initials: MS
authors.lastname: Alam
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D005054:Eugenol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
chemical_list: D000890:Anti-Infective Agents; D002273:Carcinogens; D005054:Eugenol; D015127:9,10-Dimethyl-1,2-benzanthracene; D009955:Ornithine Decarboxylase; D005978:Glutathione