CRC cells as wild-type (HCT-116 WT) or p53-deficient (HCT-116 p53-/-) were cultured using multicellular tumor microenvironment (TME) cultures containing T-lymphocytes and fibroblasts to elucidate the role of p53/Sirt-1 modulation in resveratrol’s concentration-dependent, pro-apoptotic, and thus anti-cancer effects. This evidence concerns the gene TP53 and cancer.