Ja. Sokoloski et al., INDUCTION OF THE DIFFERENTIATION OF HL-60 PROMYELOCYTIC LEUKEMIA-CELLS BY CURCUMIN IN COMBINATION WITH LOW-LEVELS OF VITAMIN-D-3, Oncology research, 9(1), 1997, pp. 31-39
Previous studies have shown that an antisense phosphorothioate oligonu
cleotide to the Rel A subunit of NF-kappa B, as well as vitamin E and
related antioxidants, significantly enhanced the differentiation of HL
-60 leukemia cells when combined with low levers of 1 alpha,25-dihydro
xyvitamin D-3 (vitamin D-3), an effect accompanied by a marked inhibit
ion of the transcription factor, NF-kappa B. Curcumin, a potent inhibi
tor of tumor promotion and of tumor cell growth, has also been shown t
o have antioxidant properties and to inhibit NF-kappa B. To ascertain
whether curcumin would also enhance the differentiation of HL-60 leuke
mia cells produced by vitamin D-3, presumably by interfering with NF-k
appa B activity, the effects of curcumin on the differentiation of HL-
60 cells produced by low levels of vitamin D-3 were measured. Curcumin
used alone did not produce a significant degree of differentiation of
HL-60 cells; however, this agent markedly enhanced the expression of
differentiation markers induced by low levels of vitamin D-3. Curcumin
also increased the differentiation of HL-60 cells when combined with
vitamin D analogues (I,25 dihydroxy-16-ene-23-yne vitamin D-3 and 1,25
-dihydroxy-16-ene vitamin D-3) that share the receptor binding propert
ies of vitamin D-3, whereas a vitamin D analogue (1,25-dihydroxy-16,23
-diene vitamin D-3) that caused significant calcium mobilization, but
was less effective than vitamin D-3 in binding the receptor, did not c
ause the differentiation of HL-60 cells in the presence or absence of
curcumin. Several dietary compounds structurally related to curcumin (
i.e., caffeic acid, chlorogenic acid, and ferulic acid) did not increa
se the differentiation of HL-60 cells produced by vitamin D-3. However
, the more lipophilic ethyl esters of ferulic and caffeic acid were ca
pable of inducing the differentiation of HL-60 cells, as well as enhan
cing the maturation produced by vitamin D-3. Curcumin caused a marked
reduction in NF-kappa B activity in nuclear extracts of HL-60 cells ex
posed to this agent in the presence or absence of vitamin D-3, support
ing the possibility that NF-kappa B may be a factor in the regulation
of the state of differentiation of leukemia cells.