By negatively regulating RB, MDM2 increases DNMT3A activity and DNA methylation-dependent silencing of tumor suppressor genes [29], as depicted in Figure 6C. In our present work, we observed that MDM2 downregulation in HT-29 colon cancer cells (Figure 5B) is indeed associated with RB1 upregulation upon 5-ISA-fortified lettuce extracts (Figure 4C). This evidence concerns the gene DNMT3A and colonic neoplasm.