Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line

Int J Nanomedicine. 2014 Jan 16:9:527-38. doi: 10.2147/IJN.S54346. eCollection 2014.

Abstract

This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.

Keywords: apoptosis; cell cycle arrest; mitochondrial pathway; zerumbone-loaded nanostructured lipid carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Apoptosis / drug effects
  • Caspases / metabolism
  • DNA Fragmentation / drug effects
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Jurkat Cells
  • Leukemia, T-Cell / drug therapy*
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • Lipids / chemistry
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological
  • Nanomedicine
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry*
  • Nanostructures / ultrastructure
  • Sesquiterpenes / administration & dosage*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Lipids
  • Sesquiterpenes
  • zerumbone
  • Caspases