Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis.

BACKGROUND: The combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis. METHODS: The mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated. RESULTS: The morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol. CONCLUSION: The study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes

Effects of curcumin and resveratrol treatments for 22 weeks on the enzyme activities of caspase 3 and caspase 9 in lungs during benzo[a]pyrene induced lung carcinogenesis.

<p>n = 10 Data are expressed in Mean ± S.D.</p>b<p>P<0.01 and ^cP<0.001 by Least Significance Difference test when values are compared with normal control group.</p>x<p>P<0.05, ^yP<0.01, ^zP<0.001 by Least Significance Difference test when values of Groups III, IV & V are compared with Group II.</p

Macroscopic view of lungs.

<p>[a] normal lung [b] Benzo[a]pyrene treated showing angeogenic lesions and marked inflammation [c] Benzo[a]pyrene treated lung showing tumors [close up] [d] Benzo[a]pyrene treated lung showing tumor, [e] Bezo[a]pyrene + Curcumin [f] Benzo[a]pyrene + Resveratrol [g] Benzo[a]pyrene +Curcumin + Resveratrol.</p