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: Bruna Braga Dantas, Gláucia Veríssimo Faheina-Martins, Tangbadioa Hervé Coulidiati, Caio César Barbosa Bomfim, Celidarque da Silva Dias, José Maria Barbosa-Filho, Demetrius Antônio Machado Araújo
• Journal: Journal of natural medicines (J Nat Med) Vol. 69 Issue 2 Pg. 218-23 (Apr 2015) ISSN: 1861-0293 [Electronic] Japan
• PMID: 25616501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antineoplastic Agents, Phytogenic
• Isoquinolines
• Plant Extracts
• curine

Topics

• Annexin A5
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Survival (drug effects)
• HL-60 Cells
• HT29 Cells
• Humans
• Isoquinolines (isolation & purification, pharmacology, therapeutic use)
• Leukemia, Promyelocytic, Acute (drug therapy)
• Leukocytes, Mononuclear (drug effects)
• Membrane Potential, Mitochondrial (drug effects)
• Menispermaceae (chemistry)
• Phytotherapy
• Plant Extracts (chemistry, pharmacology, therapeutic use)