title: Effect of cloretazine (VNP40101M) on acute myeloid leukaemia blast cells in vitro as a single agent and combined with cytarabine and daunorubicin.
abstract: We have investigated the effect of cloretazine (VNP40101M or Laromustine), a novel sulfonylhydrazine alkylating agent with significant antileukaemic activity, alone, or combined with cytarabine or daunorubicin, on the proliferation, viability and apoptosis of cell lines and acute myeloid leukaemia blast cells in vitro. Cloretazine alone induced a concentration-dependent inhibition of proliferation, reduction in cell viability and an increase in apoptosis in all samples tested. Combinations of cloretazine with varying concentrations of cytarabine or daunorubicin further enhanced these inhibitory effects, suggesting VNP40101M may have a role in combined low dose chemotherapy regimes especially in the elderly.
authors.affiliation: Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Morris
authors.forename: Julie A
authors.initials: JA
authors.lastname: Adams
authors.forename: John A
authors.initials: JA
authors.lastname: Liu Yin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D006834:Hydrazines; D013449:Sulfonamides; D003561:Cytarabine; C483604:laromustine; D003630:Daunorubicin