Effects of homo-aza-steroids on acute non-lymphocytic leukaemia cell proliferation in vitro.
Homo-aza-steroids (modified steroid molecules) in their esterified forms have been used extensively as carrier molecules of alkylating agents against several neoplastic malignancies in vivo and in vitro. We studied the effects of two homo-aza-steroid carrier molecules alone, namely 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam (compound 1) and 13 alpha-amino-13,17-seco-1,3,5-estratrien-17-oic- 13,17-lactam (compound 2), on human acute non-lymphocytic leukaemia cell proliferation in vitro. We used peripheral blood samples from 27 untreated ANLL patients (eight M1, four M2, two M3, six M4, three M5a, two M5b and two M6, according to FAB criteria). Proliferative activity was estimated by using thymidine uptake and the percentage of cells in metaphase in 24, 48 and 72 h of culture. Exposure of human leukaemic blasts with either of the two compounds resulted in enhanced cell proliferation in M1, M2, M4, M6 and M5a (only by compound 2) cases, whereas there was no significant effect in the M3 and M5b cases. Our results indicate that the two compounds tested exhibit stimulatory effect on cell proliferation, particularly in blast cells possessing a relatively smaller degree of differentiation (M1 and M6 cases exhibiting CD34 and CD7). Further research is needed to study the cell growth effect and the therapeutic potential of these steroid molecules in human blood malignancies in vitro and in vivo.
Institute of Nuclear Technology-Radiation Protection, N.C.S.R. Demokritos, Athens, Greece.
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Trafalis
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Sambani
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Kapsimali
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Economidou
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Politis
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Catsoulacos
D001378:Azasteroids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002871:Chromosome Banding; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008940:Mitotic Index; D012854:Sister Chromatid Exchange; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism
D001378:Azasteroids; D004337:Drug Carriers; D013936:Thymidine