Combination of Resveratrol and Quercetin Causes Cell Growth Inhibition, DNA Damage, Cell Cycle Arrest, and Apoptosis in Oral Cancer Cells

Resveratrol and quercetin alone are well reported to have anticancer potential, but their combination studies are very inadequate. We have examined their combination in Cal-33 and SCC-15 oral cancer cells (OCCs) and noncancerous HEK-293 cells. Combination of 10 mu M concentration of each resveratrol and quercetin brought additive effect on cellular growth, DNA damage, S-phase cell cycle arrest, and cell death in Cal-33 cells but not in the HEK-293 cells. Augmentation of the cell cycle regulatory protein, Cyclin E, and downregulation of Cyclin A possibly caused S-phase arrest in Cal-33 cancer cells. Comet formation and presence of gamma-H2AX foci confirmed DNA damage, and cleavage of PARP1 and upregulation in Bax level specified apoptosis after combined treatment. Ratio of transcription activation and repression histone marks was found increased after alone as well as combined treatment. Histone deacetylase (HDAC)1, HDAC3, and HDAC8 were downregulated by resveratrol alone and combined treatment. Conclusively, combination of resveratrol and quercetin brings cell growth inhibition, DNA damage, and cell cycle arrest in OCCs but not in normal cells. Additionally, combined treatment causes downregulation of HDACs and apoptosis in cancer cells and it could be an incisive strategy against oral cancer.