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

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

Author information

1
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq.
2
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
3
Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia.
4
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq.
5
Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
6
Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia ; College of Medical Laboratory Technology, Institute for Medical Research, Kuala Lumpur, Malaysia.

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

PMID:
24549090
PMCID:
PMC3897324
DOI:
10.2147/IJN.S54346
[Indexed for MEDLINE]
Free PMC Article

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