title: Thymoquinone inhibits murine leukemia WEHI-3 cells in vivo and in vitro.
abstract: BACKGROUND
  Thymoquinone is an active ingredient isolated from Nigella sativa (Black Seed). This study aimed to evaluate the in vitro and in vivo anti-leukemic effects of thymoquinone on WEHI-3 cells.
  
  
  RESULTS
  The cytotoxic effect of thymoquinone was assessed using an MTT assay, while the inhibitory effect of thymoquinone on murine WEHI-3 cell growth was due to the induction of apoptosis, as evidenced by chromatin condensation dye, Hoechst 33342 and acridine orange/propidium iodide fluorescent staining. In addition, Annexin V staining for early apoptosis was performed using flowcytometric analysis. Apoptosis was found to be associated with the cell cycle arrest at the S phase. Expression of Bax, Bcl2 and HSP 70 proteins were observed by western blotting. The effects of thymoquinone on BALB/c mice injected with WEHI-3 cells were indicated by the decrease in the body, spleen and liver weights of the animal, as compared to the control.
  
  
  CONCLUSIONS
  Thymoquinone promoted natural killer cell activities. This compound showed high toxicity against WEHI-3 cell line which was confirmed by an increase of the early apoptosis, followed by up-regulation of the anti-apoptotic protein, Bcl2, and down-regulation of the apoptotic protein, Bax. On the other hand, high reduction of the spleen and liver weight, and significant histopathology study of spleen and liver confirmed that thymoquinone inhibited WEHI-3 growth in the BALB/c mice. Results from this study highlight the potential of thymoquinone to be developed as an anti-leukemic agent.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Landa Zeenelabdin Ali
authors.initials: LZ
authors.lastname: Salim
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Center for Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, Center for Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.affiliation: Department of Pathology, Faculty of Medicine, SEGi University, Petaling Jaya, Malaysia.
authors.forename: Karim
authors.initials: K
authors.lastname: Al-Jashamy
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Center for Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Dehghan
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohamed Yousif
authors.initials: MY
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Fatima Abd Elmutaal Ahmed
authors.initials: FA
authors.lastname: Omer
authors.affiliation: Medical Research Centre, Jazan University, Jazan, Saudi Arabia.
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D031881:Nigella sativa / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology / Q000473:pathology; D014184:Transplantation, Homologous; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C003466:thymoquinone