Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention

Significance One hypothetical pathway leading to oncogenic transformation involves a transient phase of tetraploidization, followed by asymmetric cell divisions, aneuploidy, and genomic instability. By means of a pharmacological screen, we identified resveratrol and salicylate as compounds that kill tetraploid cells more efficiently than their parental diploid counterparts. Resveratrol and salicylate reduced the frequency of tetraploid cells arising from primary epithelial cell cultures exposed to mitotic inhibitors. In a mouse model of intestinal oncogenesis resembling familial adenomatous polyposis both resveratrol and aspirin, the salicylate prodrug, reduced the frequency of tetraploid cells accumulating in the gut, correlating with their chemopreventive action. These findings underscore the relationship between tetraploidy and oncogenesis as they unveil the mechanisms through which aspirin can prevent the development of cancer.