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.


CONCLUSIONS
The study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes.
Department of Biophysics, Post Graduate Institute of Medical Education and Research [PGIMER], Chandigarh, India.
Anshoo
A
Malhotra
Department of Biophysics, Panjab University, Chandigarh, India.
Praveen
P
Nair
Department of Biophysics, Panjab University, Chandigarh, India.
Devinder Kumar
DK
Dhawan
D000704:Analysis of Variance; D000818:Animals; D001564:Benzo(a)pyrene; D015153:Blotting, Western; D002250:Carbon Radioisotopes / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000517:prevention & control*; D051379:Mice; D010766:Phosphorylation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002250:Carbon Radioisotopes; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene; D003474:Curcumin; D000077185:Resveratrol