CURCUMIN INHIBITS CARCINOGEN INDUCED C-HA-RAS AND C-FOS PROTO-ONCOGENES EXPRESSION, AND PROTEIN KINASE C ACTIVITY IN MOUSE SKIN
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2010-01-15
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Chiang Mai Medical Journal
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Abstract We investigated the chemopreventive action of dietary curcumin in male Swiss albino mice 7 with 12-dimethylbenz(a) anthracene (DMBA)-initiated and 12, 0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation. At 6 weeks of age, the groups of animals were fed the control diet (modified AIN-76A) or one containing 0.2% or 1% curcumin. At 8 weeks of age, all animals, except those in the vehicle (acetone)-treated groups, received 100 ?g of DMBA dissolved in 100 ?l of acetone in a single application to the skin on their back. From 1 week after DMBA application, tumor promoter (2.5 ?g of TPA dissolved in 100 ?l of acetone) was applied to the same areas of the mouse skin twice a week for 26 weeks. All groups continued their respective dietary regimen until the termination of the experiment. The results showed that dietary administration at 0.2% or 1% curcumin significantly inhibited the number of tumors per mouse and the tumor volume. Curcumin in the diet did not hinder the animals. Overall results demonstrated the safety as well as the anti-carcinogenic effect of dietary curcumin in mice. Using the enhanced chemiluminescence Western blotting detection system (Amersham), we found a relative increase in the cellular oncogene of FBJ murine osteogenic sarcoma virus (c-fos) and cellular oncogene of Harvey rat sarcoma virus (c-Ha-ras) proteins in tumorous skin. This was compared with the non-tumorous skin isolated from the same mouse. Dot blot analysis of c-Ha-ras and c-fos RNA transcripts in the tumorous and non-tomorous skin was also determined. Both cellular oncogenes exhibited higher levels in tumorous rather than normal skin. The enhanced expression of ras and fos proto-oncogenes in skin tumors in DMBA and TPA-treated animals was decreased by dietary curcumin. Also, it was found that the curcumin inhibited protein kinase C (PKC) activities in mouse epidermal extracts in a dose dependent manner. Chiang Mai Med Bull 2001;40(3):127-137.
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Chiang Mai Medical Journal; Vol.40 No.3 September 2001(pages 111 - 155); 127 - 137