Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin.
BACKGROUND
We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding.


RESULTS
Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham).


CONCLUSIONS
Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin.
Limtrakul
P
P
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand 50200. plimtrak@mail.med.cmu.ac.th
Anuchapreeda
S
S
Lipigorngoson
S
S
Dunn
F W
FW
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics; D011905:Genes, ras / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate