Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway.
BACKGROUND
Eugenol is the active component of essential oil isolated from clove (Syzigium aromaticum). Eugenol has antimutagenic, antigenotoxic, anti-inflammatory properties. The anticarcinogenic effect of eugenol was evident in different types of cell lines. However, its anticarcinogenic effect in in vivo has not yet been fully explored.


OBJECTIVE
The aim of this study is to evaluate the chemopreventive potential of eugenol in an experimental skin carcinogenesis mice model system.


METHODS
Skin tumor was induced by topical application of DMBA croton oil in Swiss mice. To assess the chemopreventive potential of eugenol, it was orally administered 15 days prior carcinogen treatment. The development of skin carcinogenesis was confirmed by histopathological analysis. Cellular proliferation and apoptosis in the skin tumor were analyzed by in situ cellular proliferation and in situ cell death assay. Expression of some proliferation and apoptosis associated genes was analyzed by RT-PCR and protein expression was analyzed by Western blot.


RESULTS
Reduction in incidence and sizes of skin tumors along with overall increase in survival of mice were seen due to eugenol treatment. Restriction of skin carcinogenesis at the dysplastic stage along with reduced rate of cellular proliferation and increase in apoptosis were evident in eugenol treated skin tumors. Eugenol treatment led to the downregulation of c-Myc, H-ras and Bcl2 expression along with upregulation of P53, Bax and active Caspase-3 expression in the skin lesions.


CONCLUSIONS
Restriction of skin carcinogenesis at dysplastic stage by eugenol was due to attenuation of c-Myc, H-ras and modification of some p53 associated gene expression.
Pal
Debolina
D
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India.
Banerjee
Sarmistha
S
Mukherjee
Sudeshna
S
Roy
Anup
A
Panda
Chinmay K
CK
Das
Sukta
S
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects*; D003436:Croton Oil / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D005054:Eugenol / Q000494:pharmacology*; D005260:Female; D016259:Genes, myc / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000032:analysis
D016588:Anticarcinogenic Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D005054:Eugenol; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D053148:Caspase 3