title: pecific nutrient combination effects on tax, NF- κB and MMP-9 in human T-cell lymphotropic virus -1 positive malignant T-lymphocytes.
abstract: BACKGROUND
  Adult T-cell Leukemia (ATL) is a disease with no known cure. The disease manifests itself as an aggressive proliferation of CD4+ cells with the human T-cell Lymphotropic virus type 1 (HTLV-1). The leukemogenesis of the virus is mainly attributed to the viral oncoprotein. Tax activates the Nuclear Factor kappa B (NF-κB) which stimulates the activity and expression of the matrix metalloproteinase-9 (MMP-9). The objective of this study was to investigate the efficacy of a specific nutrient synergy (SNS) on proliferation, Tax expression, NF-κB levels as well as on MMP-9 activity and expression both at the transcriptional and translational levels in two HTLV-1 positive cell lines, HuT-102 and C91-PL at 48h and 96h of incubation. Cytotoxicity of Epigallocatechin-3-gallate (EGCG) was assayed using CytoTox 96 Non-radioactive and proliferation was measured using Cell Titer96TM Nonradioactive Cell Proliferation kit (MTT- based assay). Enzyme linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA) were used to assess the effect of SNS on NF-κB mobility. Zymography was used to determine the effects of SNS on the activity and secretion of MMP-9. The expression of MMP-9 was done using RT-PCR at the translational level and Immunoblotting at the transcriptional level.
  
  
  RESULTS
  A significant inhibition of proliferation was seen in both cell lines starting at a concentration of 200μg/ml and in a dose dependent manner. SNS induced a dose dependent decrease in Tax expression, which was paralleled by a down-regulation of the nuclearization of NF-κB. This culminated in the inhibition of the activity of MMP-9 and their expression both at the transcriptional and translational levels.
  
  
  CONCLUSIONS
  The results of this study indicate that a specific nutrient synergy targeted multiple levels pertinent to the progression of ATL. Its activity was mediated through the NF-κB pathway, and hence has the potential to be integrated in the treatment of this disease as a natural potent anticancer agent.
authors.forename: Steve
authors.initials: S
authors.lastname: Harakeh
authors.forename: Rania
authors.initials: R
authors.lastname: Azar
authors.forename: Esam
authors.initials: E
authors.lastname: Azhar
authors.forename: Ghazi A
authors.initials: GA
authors.lastname: Damanhouri
authors.forename: Mourad
authors.initials: M
authors.lastname: Assidi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abu-Elmagd
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Alqahtani
authors.forename: Taha
authors.initials: T
authors.lastname: Kumosani
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Niedzwiecki
authors.forename: Mathias
authors.initials: M
authors.lastname: Rath
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Hejin
authors.forename: Elie
authors.initials: E
authors.lastname: Barbour
authors.forename: Mona
authors.initials: M
authors.lastname: Diab-Assaf
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D063646:Carcinogenesis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015490:HTLV-I Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D016356:Gene Products, tax; D016328:NF-kappa B; C514970:tax protein, Human T-lymphotrophic virus 1; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9