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

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 527 - 538
• Main Authors: Rahman, Heshu Sulaiman, Rasedee, Abdullah, Abdul, Ahmad Bustamam, Zeenathul, Nazariah Allaudin, Othman, Hemn Hassan, Yeap, Swee Keong, How, Chee Wun, Hafiza, Wan Abd Ghani Wan Nor
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2014; Dove Medical Press
• Subjects: Analysis; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Apoptosis - drug effects; Caspases - metabolism; Complications and side effects; DNA Fragmentation - drug effects; Dosage and administration; Drug Carriers - chemistry; Drug Delivery Systems; Drug therapy; 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; Liposomes; Lymphocytic leukemia; Mitochondria - drug effects; Mitochondria - metabolism; Models, Biological; Nanomedicine; Nanoparticles; Nanostructures - administration & dosage; Nanostructures - chemistry; Nanostructures - ultrastructure; Original Research; Physiological aspects; Sesquiterpenes - administration & dosage; Malaysia; mitochondrial pathway; apoptosis; cell cycle arrest; zerumbone-loaded nanostructured lipid carrier
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S54346

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.