Induction of apoptosis in megakaryocytic leukemia cell lines by MX2, a morpholino anthracycline.
Leukemia with megakaryocytic involvement has a poor prognosis. MX2 is a new morpholino anthracycline that is effective against various leukemic cell lines. This study examined the antitumor activity of MX2 against human megakaryocytic cell lines, including CMK, CMK11-5, MEG-01, and UT-7, and investigated the role of apoptosis in the cytotoxicity of this drug. To quantify the extent of apoptosis induced by MX2, we used the in situ terminal deoxynucleotide transferase assay and the histone-associated DNA fragmentation assay. The cytotoxic effect of MX2 on CMK cells was reduced by various inhibitors of apoptosis. To our knowledge, this is the first report showing that apoptosis is involved in the killing of megakaryocytic cell lines by an antileukemic agent. We suggest that MX2 may be useful for the treatment of megakaryocytic leukemia.
Katsurada
T
T
First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan.
Adachi
M
M
Kido
H
H
Date
M
M
Kishimoto
Y
Y
Yamanaka
Y
Y
Kimura
T
T
Fukuhara
S
S
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D002360:Carubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007947:Leukemia, Megakaryoblastic, Acute / Q000473:pathology*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D008854:Microscopy, Electron; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; C053537:morpholinoanthracycline MX2; D017828:Rifabutin; D015759:Ionomycin; C020754:herbimycin; D002360:Carubicin; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine