Document Detail


Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice.
MedLine Citation:
PMID:  15122579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 micromol) 24 hr before application of dimethylbenz[a]anthracene (0.2 micromol) 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 micromol) 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.
Authors:
Akira Murakami; Takuji Tanaka; Ji-Yoon Lee; Young-Joon Surh; Ha Won Kim; Kyuichi Kawabata; Yoshimasa Nakamura; Suratwadee Jiwajinda; Hajime Ohigashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  110     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-05-03     Completed Date:  2004-06-15     Revised Date:  2012-05-28    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-90     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Affiliation:
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. cancer@kais.kyoto-a.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / pharmacology*
Cyclooxygenase 2
Enzyme Induction / drug effects
Female
Glutathione S-Transferase pi
Glutathione Transferase / genetics
Isoenzymes / antagonists & inhibitors,  genetics
Mice
Mice, Inbred ICR
Mitogen-Activated Protein Kinases / metabolism
NAD(P)H Dehydrogenase (Quinone) / genetics
Oxidative Stress / drug effects
Phosphorylation
Prostaglandin-Endoperoxide Synthases
Sesquiterpenes / pharmacology*
Skin Neoplasms / prevention & control*
Tetradecanoylphorbol Acetate / pharmacology
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Isoenzymes; 0/Sesquiterpenes; 16561-29-8/Tetradecanoylphorbol Acetate; 471-05-6/zerumbone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human; EC 2.5.1.18/Glutathione S-Transferase pi; EC 2.5.1.18/Glutathione Transferase; EC 2.5.1.18/Gstp1 protein, mouse; EC 2.7.11.24/Mitogen-Activated Protein Kinases

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