Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells

Dietary flavonoids were found to be antiproliferative for human colon cancer cells, Caco-2 and HT-29, and rat nontransformed intestinal crypt cells, IEC-6. The antiproliferative potency was found to be structure-dependent. We report here a correlation between the antiproliferative potency of these flavonoids and their ability to inhibit cellular accumulation of ascorbic acid (vitamin C). Caco-2, HT-29 and IEC-6 cells were found to accumulate ascorbic acid in a sodium-dependent fashion although some ascorbic acid may also enter the cells through sodium-independent mechanisms. Flavonoids that have been found to be antiproliferative, quercetin and genistein, inhibited the accumulation of ascorbic acid. The inhibition was dose-dependent and could be observed after as short as 10-min of incubation. The degree of inhibition of accumulation was more during rapid cell division as compared to post-confluency Caco-2 cells. Flavonoids that were found to show little antiproliferative effect, naringenin and catechin, also had little effect on ascorbic acid accumulation. The antiproliferative property of flavonoids could be linked to their ascorbic acid deprivation property.