title: Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells.
abstract: Rapamycin and its derivatives have been proposed in the treatment of leukemia based on their cytostatic effects, but their possible role in differentiation therapy is less explored. The aim of the present study was to investigate the possible beneficial effects of the combination of rapamycin and dimethyl sulfoxide (DMSO) on growth arrest and differentiation of acute myelogenous leukemia (AML) cells. In myeloblastic HL-60, promyelocytic NB4, monocytic U937, immature KG-1 and erythro-megakaryocytic K562 cell lines, rapamycin alone had modest inhibitory effects, DMSO inhibited proliferation in a dose-dependent manner, and the combination of rapamycin and DMSO reduced the number of viable cells significantly more than either agent alone. In NB4 cells, rapamycin had no statistically significant effects on the DMSO-mediated increase in expression of CD11b, but increased apoptosis. These results demonstrate that rapamycin enhances DMSO-mediated growth arrest, and suggest that mTOR (mammalian target of rapamycin) inhibitors may have beneficial effects in differentiation therapy of AML.
authors.affiliation: Department of Physiology, University of Zagreb, Zagreb, Croatia.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Lalic
authors.forename: Vesna
authors.initials: V
authors.lastname: Lukinovic-Skudar
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Banfic
authors.forename: Dora
authors.initials: D
authors.lastname: Visnjic
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D004121:Dimethyl Sulfoxide