Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction

J Nat Med. 2015 Apr;69(2):218-23. doi: 10.1007/s11418-014-0881-5. Epub 2015 Jan 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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