[Induction differentiation by a new third generation retinoid R9158 on human acute promyelocytic leukemia cell line,...

In order to investigate the differentiation of 3',5'-ditertiary-butiary-4'-methoxy-carboxyl chalcone (R9158) on the acute promyelocytic leukemia NB4 cells.

By inditifying the function, morphology and karyotype of NB4 cells induced by R9158.

Our results showed that R9158 or all-trans retinoic acid (RA) significantly inhibited the growth and colony formation of acute promyelocytic leukemia NB4 cells, while NBT-reduction (a functional differentiation marker of granulocytic) was dramatically increased when the cells were exposed to R9158 at 10(-9)-10(-6) mol/L, and the NBT positive cells reached about 97.5% at 10(-6) mol/L after 6 days expouse. The ED50 of NBT-reduction was achieved at concentration of 3.9 x 10(-9) mol/L and 2.8 x 10(-9) mol/L for R9158 and RA, respectively. Morphologically, most of the cells induced by R9158 and RA at 10(-6) mol/L were in the myelocytic or metamyelocytic stage and a few cells were in the banded or segmented stage. Cytogenetic analysis revealed that the karyotype of NB4 cells was subtetraploid and the chromosome numbers were in the range of 71-99, when NB4 cells were treated with R9158 or RA for 3-6 days, the abnormal polyploid chromosome numbers decreased to 72.9 +/- 6.9 (P < 0.01) or 68.5 +/- 7.0 (P < 0.01), but the t(15;17) translation did not disappear.

R9158 has significant effects on the differentiation of NB4 cells.