INDUCTION OF THE DIFFERENTIATION OF HL-60 PROMYELOCYTIC LEUKEMIA-CELLS BY VITAMIN-E AND OTHER ANTIOXIDANTS IN COMBINATION WITH LOW-LEVELS OF VITAMIN-D-3 - POSSIBLE RELATIONSHIP TO NF-KAPPA-B

Epidemiological studies have provided evidence that diets rich in anti oxidant nutrients may reduce the risk of cancer. To evaluate the possi bility that dietary phytochemicals with antioxidant potential would cr eate an environment capable of affecting the differentiation of HL-60 leukemia cells, we measured the effects of vitamin E and other dietary antioxidants on the differentiation produced by low levels of vitamin D-3 and analogs thereof. Vitamin E succinate and other antioxidant co mpounds (ie butylated hydroxyanisole, beta-carotene and lipoic acid) u sed alone had no significant effect on the differentiation of HL-60 ce lls; however, these agents markedly increased the differentiation prod uced by vitamin D-3. Previous studies from this laboratory have shown that a sequence-specific antisense phosphorothioate oligonucleotide to the Rel A subunit of NF-kappa B enhanced the differentiation of HL-60 cells produced by several inducing agents. Consistent with these obse rvations, vitamin E succinate caused a marked reduction in the nuclear content of NF-kappa B bath in the presence and absence of vitamin D-3 . These findings suggest that MF-kappa B may be a factor in regulating the differentiation of myeloid leukemia cells. The results also indic ate that combinations of vitamin D-3 and analogs thereof with dietary antioxidants may be useful in overcoming the differentiation block pre sent in acute promyelocytic leukemia cells.