[Induction differentiation by a new third generation retinoid R9158 on human acute promyelocytic leukemia cell line, NB4].
OBJECTIVE
In order to investigate the differentiation of 3',5'-ditertiary-butiary-4'-methoxy-carboxyl chalcone (R9158) on the acute promyelocytic leukemia NB4 cells.


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


RESULTS
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.


CONCLUSIONS
R9158 has significant effects on the differentiation of NB4 cells.
He
X
X
Institute of Materia Medica, CAMS and PUMC, Beijing 100050.
Han
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R
D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D047188:Chalcones; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D012176:Retinoids / Q000494:pharmacology*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
C442847:3',5'-ditertiary-butiary-4'-methoxycarboxylchalcone; D000970:Antineoplastic Agents; D047188:Chalcones; D012176:Retinoids; D002599:Chalcone