Dihydropyridine calcium channel blockers inhibit ascorbic acid accumulation in human intestinal Caco-2 cells.

We investigated the effect of commonly used medications on the accumulation of ascorbic acid in human intestinal Caco-2 cells. Although ascorbic acid is negatively charged at physiological pH, anionic compounds including drugs and metabolites had little effect on its accumulation. On the other hand, hydrophobic 1,4-dihydropyridine compounds (nifedipine and nicardipine), but not other structurally unrelated calcium channel blockers, were found to be potent inhibitors. They inhibited both Na+-dependent and Na+-independent (K+ substituting Na+) accumulation of ascorbic acid. The inhibition was non-competitive with a Ki of 108 microM and 9 microM for nifedipine and nicardipine, respectively. The efflux of ascorbic acid from cells was not affected. Previously, we reported a similar inhibition of ascorbic acid accumulation by estrogens. When nifedipine and estrogens were included in the buffer together, the combined inhibitory effect was less than additive implying that they may act through the same mechanism. The potential clinical significance of dihydropyridine usage on ascorbic acid status in human needs to be considered.

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.