title: Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction.
abstract: Curine is a natural alkaloid isolated from Chondrodendron platyphyllum and it has been reported that this alkaloid has vasodilatory and anti-inflammatory effects. The aim of this study is to analyze the cytotoxic effects of curine in cancer cell lines HL-60, K562, and HT-29, and in primary cultures of peripheral blood mononuclear cells (PBMC). Cells were treated with curine (from 3 to 15 µM) for 24 and 48 h. Cell viability was analyzed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry with propidium iodide (PI) assay. To assess the type of cell death induced in HL-60, the cell cycle, morphological, and biochemical alterations were analyzed, which were determined by differential staining with acridine orange/ethidium bromide, and annexin V/PI double-labeling and change in mitochondrial membrane potential assays. Curine demonstrated a potent cytotoxic effect on leukemic cell lines (HL-60 and K562). Its cytotoxic effects in HL-60 cells was related to plasma membrane damage and cell cycle arrest at the G1 phase from 43.4 ± 1.0 to 56.7 ± 1.4 % (p < 0.05). Curine (15 μM) also increased the apoptotic cells number by around 60 % in HL-60 cells and caused phosphatidylserine externalization, inducing about 57 % of apoptosis. Moreover, this alkaloid provoked 20 % of mitochondrial membrane depolarization. We conclude that curine presented a cytotoxic effect and induced apoptosis in HL-60 cells. Thus, it can be considered a promising pharmacological drug.
authors.affiliation: Department of Biotechnology, Center of Biotechnology, Federal University of Paraíba, Cidade Universitária, Campus I, 58051-900, João Pessoa, PB, Brazil.
authors.forename: Bruna Braga
authors.initials: BB
authors.lastname: Dantas
authors.forename: Gláucia Veríssimo
authors.initials: GV
authors.lastname: Faheina-Martins
authors.forename: Tangbadioa Hervé
authors.initials: TH
authors.lastname: Coulidiati
authors.forename: Caio César Barbosa
authors.initials: CC
authors.lastname: Bomfim
authors.forename: Celidarque
authors.initials: C
authors.lastname: da Silva Dias
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: Demetrius Antônio Machado
authors.initials: DA
authors.lastname: Araújo
mesh_terms: D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D029583:Menispermaceae / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; D010936:Plant Extracts; C470478:curine