title: Comparative cytotoxicity of dimethylamide-crotonin in the promyelocytic leukemia cell line (HL60) and human peripheral blood mononuclear cells.
abstract: Dehydrocrotonin (DHC) is a diterpene lactone obtained from Croton cajucara (Sacaca). Dimethylamide-crotonin (DCR), a DHC derivative, has a similar inhibitory effect on leukemic HL60 cells than its parent compound evaluated by different endpoints of cytotoxicity. No cytotoxicity or morphological alterations associated with apoptosis were detected in human peripheral blood mononuclear cells (PBMC) after treatment with up to 400 micro M DCR in presence of phytohemaglutinin (5 micro g/ml). Based on morphological changes and the pattern of DNA fragmentation, DHC and DCR were found to induce apoptosis and terminal differentiation (assessed by nitro blue tetrazolium reduction) in HL60 cells, but these compounds did not show any toxic effect in PBMC. Thus, DCR and DHC inhibit HL60 cell growth in vitro partly by inducing apoptosis and cell differentiation, but does not cause serious damage to immune cells according to our experimental conditions.
authors.affiliation: Departamento de Bioqui;mica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP, 13083-970, Brazil.
authors.forename: Maristella Conte
authors.initials: MC
authors.lastname: Anazetti
authors.forename: Patricia Silva
authors.initials: PS
authors.lastname: Melo
authors.forename: Nelson
authors.initials: N
authors.lastname: Durán
authors.forename: Marcela
authors.initials: M
authors.lastname: Haun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000633:toxicity*; D045785:Diterpenes, Clerodane; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010946:Plants, Medicinal
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D007783:Lactones; C103060:dehydrocrotonin; C475025:dimethylamide-crotonin; D009580:Nitroblue Tetrazolium