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Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice

Cited 123 time in Web of Science Cited 143 time in Scopus
Authors
Murakami, Akira; Tanaka, Takuji; Lee, Ji‐Yoon; Surh, Young‐Joon; Kim, Ha Won; Kawabata, Kyuichi; Nakamura, Yoshimasa; Jiwajinda, Suratwadee; Ohigashi, Hajime
Issue Date
2004-07
Citation
International Journal of Cancer, Vol.110 No.4, pp.481-490
Keywords
zerumbone12-O-teradecanoylphorbol-13-acetate7,12-dimethylbenz[a]anthracenexenobiotic enzymecyclooxygense-2oxidative stress
Abstract
We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti-tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2-stage carcinogenesis model. A single topical pretreatment to mouse skin (2 mumol) 24 hr before application of dimethylbenz[a]anthracene (0.2 mumol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post-initiation phase reduced the number of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol)-induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 mumol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase-1, glutathione S-transferase-P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome P450 1A1 or 1B1. Further, it diminished TPA-induced cyclooxygenase-2 protein expression and phosphorylation of extracellular signal-regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application-induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti-oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways. (C) 2004 Wiley-Liss, Inc.
ISSN
0020-7136
URI
https://hdl.handle.net/10371/172837
DOI
https://doi.org/10.1002/ijc.20175
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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