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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by
Gurpreet Kaur1, Mohammad Athar, M Sarwar Alam
1Department of Chemistry, Faculty of Science, Jamia Hamdard, New Delhi, India.
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.
Insights
Eugenol demonstrates significant protective effects against chemically induced skin cancer by reducing cell proliferation and increasing apoptosis. This natural compound also exhibits anti-inflammatory and antioxidant properties, inhibiting key markers of tumor promotion and inflammation.
Area of Science:
- Chemoprevention
- Dermatology
- Molecular Biology
Background:
- Skin cancer is a significant global health concern.
- Chemically induced skin cancer models are crucial for evaluating potential therapeutic agents.
- Eugenol, a natural compound, has shown potential biological activities.
Purpose of the Study:
- To investigate the protective efficacy of eugenol against chemically induced skin cancer.
- To elucidate the mechanistic aspects of eugenol's chemopreventive effects.
- To assess eugenol's impact on various stages of skin carcinogenesis.
Main Methods:
- Skin tumors were induced in mice using 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).
- Eugenol was administered using anti-initiation and anti-promotion protocols.
- Immunohistochemistry (PCNA, TUNEL), gene expression analysis (p53, p21WAF1), enzyme activity assays (ODC), and measurement of inflammatory markers (iNOS, COX-2, IL-6, TNF-alpha, PGE2) were performed.
Main Results:
- Eugenol pretreatment significantly delayed tumor onset and reduced tumor incidence.
- Eugenol ameliorated cell proliferation and induced apoptosis in tumor tissues.
- Eugenol inhibited key markers of tumor promotion and inflammation, including ODC activity, iNOS, COX-2, and pro-inflammatory cytokines.
- Eugenol prevented the depletion of glutathione (GSH) and antioxidant enzymes caused by TPA.
- Eugenol inhibited NF-kappaB signaling pathway.
Conclusions:
- Eugenol exhibits marked protective efficacy against chemically induced skin cancer.
- Eugenol's chemopreventive effects are attributed to its antiproliferative, anti-inflammatory, and antioxidant activities.
- Eugenol modulates key molecular pathways involved in skin carcinogenesis, including apoptosis and inflammation.
