The impact of resveratrol on cell growth and cell cycle of colon cancer cells

Resveratrol, 3, 5, 4 \u27-trihydroxy-stilbene, is a naturally occurring plant phytoalexin that has been found to have cancer preventive effects in animal models and cultured cells. In the current study, resveratrol was found to dose dependently arrest cells in S and G2/M stages of cell cycle and reduce cell number in four different colorectal cancer cell lines (SW480, HT29, DLD1, and HCT116) dose dependently when they were treated with 0 to 80 [Mu]M resveratrol for 48 hours. Further studies in SW480 cells showed that the resveratrol induced cell growth inhibition and cell cycle arrest was reversible. The present study also compared the effects of resveratrol on colon cancer cells that express wild type or mutant tumor suppressor gene p53 or adenomatous polyposis coli (APC) gene, or on cells that have deficient or proficient mismatch repair (MMR) system. When HCT 116 cells with wild type p53 (HCT116 p53+/+) and a parallel p53 knock out cell line (HCT116 p53-/-) were treated with 0 to 30 [Mu]M resveratrol for 24, 48 and 72 hours, the impact of resveratrol on growth inhibition and cell cycle arrest was similar in the two cell lines. Similarly, when MMR proficient HCT116+chr3 and MMR deficient HCT116 cells were each treated with 30 [Mu]M resveratrol they showed comparable G2/M arrest. HT29 cells with inducible expression of full length APC (HT29-APC) and a control cell line containing inducible [Beta]-galactosidase instead of full-length APC (HT29-GAL) were used to evaluate the impact of APC on cell cycle arrest by resveratrol. The induction of full length APC protein, by adding 100 [Mu]M ZnCl2 in HT29 APC cells, was verified by western blot analysis. Both HT29-APC and HT29-GAL showed a significant G2/M arrest by 80 [Mu]M resveratrol (p\u3c0.05), and the expression of wild type APC following ZnCl2 treatment of HT29-APC cells did not alter the cells sensitivity to resveratrol. In conclusion, we found that the expression of tumor suppressor full length APC in HT29 cells, depletion of p53 or restoration of MMR status in HCT 116 cells did not change the effect of resveratrol on cell growth or cell cycle