Induction of the differentiation of HL-60 promyelocytic leukemia cells by vitamin E and other antioxidants in combination with low levels of vitamin D3: possible relationship to NF-kappaB
Sokoloski, J.A.; Hodnick, W.F.; Mayne, S.T.; Cinquina, C.; Kim, C.S.; Sartorelli, A.C.
Leukemia 11(9): 1546-1553
1997
ISSN/ISBN: 0887-6924 PMID: 9305611 Document Number: 480085
Epidemiological studies have provided evidence that diets rich in antioxidant nutrients may reduce the risk of cancer. To evaluate the possibility that dietary phytochemicals with antioxidant potential would create 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 compounds (ie butylated hydroxyanisole, beta-carotene and lipoic acid) used alone had no significant effect on the differentiation of HL-60 cells; however, these agents markedly increased the differentiation produced 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 observations, vitamin E succinate caused a marked reduction in the nuclear content of NF-kappa-B both in the presence and absence of vitamin D-3. These findings suggest that NF-kappa-B may be a factor in regulating the differentiation of myeloid leukemia cells. The results also indicate that combinations of vitamin D-3 and analogs thereof with dietary antioxidants may be useful in overcoming the differentiation block present in acute promyelocytic leukemia cells.