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

Murray, Byron K.; Brown, Brita; Scherer, Philip M.; Tomer, David P.; Garvin, Kaedi R.; Hughes, Bronwyn G.; O'Neill, Kim L.

doi:10.1016/j.nutres.2006.04.005

« PreviousNutrition Research
Volume 26, Issue 4 , Pages 186-192, April 2006

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

Byron K. Murray
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA
- Corresponding author. Tel.: +1 801 422 6207; fax: +1 801 422 0519.
Brita Brown
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA
Philip M. Scherer
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA
David P. Tomer
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA
Kaedi R. Garvin
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA
Bronwyn G. Hughes
- Plant Bioactives Research Institute, 95 South Mountain Way Drive, Orem, UT 84058, USA
Kim L. O'Neill
- Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84602-5253, USA

Received 29 December 2005; received in revised form 13 April 2006; accepted 21 April 2006.

Abstract

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 α-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 G₁/S interphase, chromatin condensation, nuclear fragmentation, DNA damage, and caspase 3 activation.

Keywords: 13-cis-Retinoic acid, α-Tocopherol succinate, Colon cancer, Apoptosis, HT-29 cells