title: Amyrin esters induce cell death by apoptosis in HL-60 leukemia cells.
abstract: Four derivatives of an α,β-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,β-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3μM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.
authors.affiliation: Departament of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará 60430-270, Brazil.
authors.forename: Francisco W A
authors.initials: FW
authors.lastname: Barros
authors.forename: Paulo N
authors.initials: PN
authors.lastname: Bandeira
authors.forename: Daisy J B
authors.initials: DJ
authors.lastname: Lima
authors.forename: Assuero S
authors.initials: AS
authors.lastname: Meira
authors.forename: Silvana S
authors.initials: SS
authors.lastname: de Farias
authors.forename: Maria Rose J R
authors.initials: MR
authors.lastname: Albuquerque
authors.forename: Hélcio S
authors.initials: HS
authors.lastname: dos Santos
authors.forename: Telma L G
authors.initials: TL
authors.lastname: Lemos
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Morais
authors.forename: Letícia Veras
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Claudia do Ó
authors.initials: Cdo Ó
authors.lastname: Pessoa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D029403:Burseraceae; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D018922:HL-60 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D028321:Plant Preparations / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D028321:Plant Preparations; D009828:Oleanolic Acid; D053148:Caspase 3; C036380:beta-amyrin