Induction of Apoptosis and Cell-Cycle Arrest in Human Colon-Cancer Cells by Whole-Grain Alkylresorcinols via Activation of the p53 Pathway

Colon cancer, one of the leading causes of cancer-associated deaths, is the target of choice for nutrition-based-prevention approaches because of the direct and early contact between the active compounds and the cancerous tissues. We previously reported alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer. Here, we further investigate the anticancer mechanisms of action of ARs. Our mechanistic studies indicated that AR C15 and AR C17 exert their anticancer activities in colon-cancer cells by inducing apoptosis through PUMA upregulation and mitochondrial-pathway activation, inducing cell-cycle arrest through p21 upregulation, and inhibiting proteasome activity and Mdm2 expression. This cascade of distinct mechanisms was linked to the consequent activation and accumulation of p53. The results of treatment with p53 inhibitor further confirmed that the p53 pathway might play a very important role in AR-induced apoptosis in colon-cancer cells. Altogether these results show that AR C15 and AR C17 can specifically activate the mitochondrial pathway of apoptosis and cause cell-cycle arrest and that inhibition of p53 greatly reduces the activation of this pathway.