Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

BMC Cancer. 2001:1:1. doi: 10.1186/1471-2407-1-1. Epub 2001 Jan 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / antagonists & inhibitors
  • 9,10-Dimethyl-1,2-benzanthracene / metabolism
  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Body Weight / drug effects
  • Body Weight / genetics
  • Carcinogens / antagonists & inhibitors*
  • Carcinogens / metabolism
  • Curcumin / administration & dosage*
  • Curcumin / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Silencing / drug effects*
  • Genes, fos / drug effects*
  • Genes, fos / genetics
  • Genes, ras / drug effects*
  • Genes, ras / genetics
  • Male
  • Mice
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / genetics
  • Skin Neoplasms / prevention & control
  • Tetradecanoylphorbol Acetate / antagonists & inhibitors
  • Tetradecanoylphorbol Acetate / metabolism

Substances

  • Antineoplastic Agents
  • Carcinogens
  • 9,10-Dimethyl-1,2-benzanthracene
  • Curcumin
  • Tetradecanoylphorbol Acetate