Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells.
Some studies have shown that dietary intake of polyunsaturated fatty acids of the n-3 series may have inhibitory effect on the growth of tumor cells both in vivo and in vitro. However, the cellular and molecular mechanisms by which n-3 fatty acids reduce the growth of tumor cells remain poorly understood. In the present studies, we compared the potency of a variety of n-3 and n-6 fatty acids in modulating the apoptotic cell death in HT-29 colon cancer cells. Of all fatty acids examined, we found that docosahexaenoic acid (22:6n-3; DHA) is a potent inducer of apoptosis in a time- and dose-dependent manner. Indomethacin, a cyclooxygenase inhibitor, is ineffective in blocking the apoptosis induced by DHA, suggesting that DHA-induced apoptosis in HT-29 cells is not mediated through the cyclooxygenase pathway. In contrast, the DHA-induced apoptosis is partially reversed by a synthetic antioxidant, butylated hydroxytoluene, indicating that lipid peroxidation may be involved in apoptotic signaling pathway induced by DHA. DHA treatment decreased bcl-2 levels in association with apoptosis, whereas bax levels remained unchanged. These results suggest that decreased expression of bcl-2 by DHA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death.
Chen
Z Y
ZY
Section of Endocrinology, Nutrition and Diabetes, Boston, MA 02118, USA.
Istfan
N W
NW
D017209:Apoptosis; D015153:Blotting, Western; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002452:Cell Count; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015227:Lipid Peroxidation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D016861:Cyclooxygenase Inhibitors; D005227:Fatty Acids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002084:Butylated Hydroxytoluene; D004281:Docosahexaenoic Acids; D007213:Indomethacin