title: Antileukemic effect of zerumbone-loaded nanostructured lipid carrier in WEHI-3B cell-induced murine leukemia model.
abstract: Cancer nanotherapy is progressing rapidly with the introduction of many innovative drug delivery systems to replace conventional therapy. Although the antitumor activity of zerumbone (ZER) has been reported, there has been no information available on the effect of ZER-loaded nanostructured lipid carrier (NLC) (ZER-NLC) on murine leukemia cells. In this study, the in vitro and in vivo effects of ZER-NLC on murine leukemia induced with WEHI-3B cells were investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase activity assays showed that the growth of leukemia cells in vitro was inhibited by ZER-NLC. In addition, outcomes of histopathology, transmission electron microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the number of leukemia cells in the spleen of BALB/c leukemia mice significantly decreased after 4 weeks of oral treatment with various doses of ZER-NLC. Western blotting and reverse-transcription quantitative polymerase chain reaction assays confirmed the antileukemia effects of ZER-NLC. In conclusion, ZER-NLC was shown to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading of ZER in NLC did not compromise the anticancer effect of the compound, suggesting ZER-NLC as a promising and effective delivery system for treatment of cancers.
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 Sulaimany, Sulaimany City, 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.
authors.forename: Chee Wun
authors.initials: CW
authors.lastname: How
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: DigiCare Behavioral Research, Casa Grande, AZ, USA.
authors.forename: Max Stanley
authors.initials: MS
authors.lastname: Chartrand
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 ; Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Sheau Wei
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Veterinary Medicine, University of Sulaimany, Sulaimany City, Northern Iraq.
authors.forename: Hemn Hassan
authors.initials: HH
authors.lastname: Othman
authors.affiliation: Faculty of Science and Technology, University Kebangsaan Malaysia, Selangor, Malaysia.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ajdari
authors.affiliation: Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Farideh
authors.initials: F
authors.lastname: Namvar
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Arulselvan
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Sharida
authors.initials: S
authors.lastname: Fakurazi
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Mehrbod
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Nasibeh
authors.initials: N
authors.lastname: Daneshvar
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Hasina
authors.initials: H
authors.lastname: Begum
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D007938:Leukemia / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D012717:Sesquiterpenes; C403304:zerumbone
keywords: BALB/c mice; WEHI-3B cells; apoptosis; leukemia; mitochondrial pathway; zerumbone-loaded nanostructured lipid carrier