Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo.
Meisoindigo, a second generation derivative of indirubin, is an effective chemotherapeutic agent with very low toxicity used in the treatment of chronic myeloid leukemia. To determine the nature of this activity, the effect of a nontoxic concentration (0.72 micrograms/mL) of this compound on ML-1 human myeloblastic leukemic cells was examined. At such a concentration, differentiation induction was found to be the most pronounced drug effect. During the 3-day drug incubation period, the viable cell number remained essentially constant, with approximately 48% of the cells demonstrating a mature phenotype with increased acid phosphatase activity and nitroblue tetrazolium dye reduction. As observed with other DNA-specific agents, induction of ML-1 differentiation by meisoindigo was accompanied by the down-regulation of c-myb gene expression. These data suggest that induction of leukemic cell differentiation associated with decreased c-myb expression may be one of the mechanisms of the antitumor action of meisoindigo.
Liu
X M
XM
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
Wang
L G
LG
Li
H Y
HY
Ji
X J
XJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007211:Indoles; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; C047330:N-methylisoindigotin