Antiproliferative effect of carotenoids on human colon cancer cells without conversion to retinoic acid.

The present study employed two human colon cancer cell lines, DLD-1 and Colo 320DM, to investigate whether the provitamin A activity of carotenoids is necessary for their antitumor effect on colon cancer. Carotenoids, including alpha- and beta-carotene and canthaxanthin, significantly suppressed cell viability [measured by tetrazolium (MTT) assay], DNA synthesis (measured by [3H]thymidine uptake), and cell proliferation (measured by cell counting) and thus showed growth-inhibitory effects on both cancer cell lines. Because canthaxanthin does not have provitamin A activity, these results suggest that the carotenoid directly inhibited the cell growth. Moreover, the effective dose of retinoic acid, an active metabolite of vitamin A, was much higher than that of alpha- or beta-carotene. A retinoic acid-inducible gene, retinoic acid receptor-beta, was not enhanced in either type of cancer cell by treatment with alpha- or beta-carotene. Therefore, like canthaxanthin, alpha- and beta-carotene might also exert their tumor-suppressing effects without being converted to retinoids. These results suggest that a certain antitumor activity of carotenoids may not necessarily require their provitamin A activity.