Induction of apoptosis in HT-29 human colon adenocarcinoma cells by 13-cis-retinoic acid and vitamin E succinate

Recent studies have shown that retinoids and vitamin E are effective growth inhibitors of numerous cancer cell lines. In the present study, vitamin A derivative 13-cis-retinoic acid and alpha-tocopherol succinate were administered to HT-29 human colon adenocarcinoma cells individually or in combination for a period of 8 days. Cells treated with individual compounds for 8 days attained 80% of the control population. Cells treated with both compounds reached 25% of the control population after 4 days and less than 1% of the control population after 8 days. After 4 days, treated cells became cytostatic, with more than 50% of the cells detaching by day 8. This synergistic effect was specific only for HT-29 cells as compared with normal human colon cells. Treatment resulted in morphological and biochemical changes indicative of apoptotic cell death, including cell cycle blockage at the G(1)/S interphase, chromatin condensation, nuclear fragmentation, DNA damage, and caspase 3 activation. (c) 2006 Elsevier Inc. All rights reserved.