In this study, we evaluated for the first time the ability of AdoMet to enhance the antitumor activity of 5-FU in HCT 116 p53+/+ and in LoVo colon cancer cells by overcoming MDR and we investigated AdoMet-induced modulation of p-glycoprotein expression and NF-kB signaling downregulation. This evidence concerns the gene TP53 and colonic neoplasm.