title: Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line.
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.
authors.affiliation: 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.
authors.forename: Heshu Sulaiman
authors.initials: HS
authors.lastname: Rahman
authors.affiliation: Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Rasedee
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.affiliation: Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Nazariah Allaudin
authors.initials: NA
authors.lastname: Zeenathul
authors.affiliation: Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq.
authors.forename: Hemn Hassan
authors.initials: HH
authors.lastname: Othman
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Chee Wun
authors.initials: CW
authors.lastname: How
authors.affiliation: Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia ; College of Medical Laboratory Technology, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Wan Abd Ghani Wan Nor
authors.initials: WA
authors.lastname: Hafiza
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D050997:Nanomedicine; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D012717:Sesquiterpenes / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D012717:Sesquiterpenes; C403304:zerumbone; D020169:Caspases
keywords: apoptosis; cell cycle arrest; mitochondrial pathway; zerumbone-loaded nanostructured lipid carrier