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Inhibition of proliferation and induction of apoptosis by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide in adult T-cell leukemia cells

Show simple item record Harakeh S. Diab-Assef M. El-Sabban M. Haddadin M. Gali-Muhtasib H.
dc.contributor.editor Jul-2004 2017-10-03T15:45:37Z 2017-10-03T15:45:37Z 2004
dc.identifier 10.1016/j.cbi.2004.05.002
dc.identifier.issn 00092797
dc.description.abstract Human T-cell lymphotrophic virus type-1 (HTLV-1) is a retrovirus which causes adult T-cell leukemia (ATL), an aggressive malignancy of activated T-cells. So far, there is no proven therapy for this disease. The compound 2-benzoyl-3-phenyl-6,7-dichloro quinoxaline 1,4-dioxide (DCQ) has been shown to exhibit a wide range of antibacterial activities and to induce antiproliferation and apoptosis of human colon cancer cell lines. In the present study, we investigated the in vitro effects of DCQ in HTLV-1 positive (C91-PL and HuT-102) and negative (CEM and Jurkat) malignant T-cells. The results indicate that DCQ induced growth inhibition in all four cell lines examined in a dose-dependent manner. The inhibitory effect was mainly due to the induction of apoptosis which was verified by flow cytometry analyses and ELISA-based apoptosis assays. The role of transforming growth factor (TGF) in mediating the antiproliferative and apoptotic effects of DCQ in ATL cells was investigated. Interestingly, in three of the four cell lines used, DCQ increased the TGF-β1 transcript levels and decreased TGF-α mRNA, but did not induce changes in TGF-β2 expression. DCQ treatment also induced an upregulation of p53 and p21 protein levels, key mediators of cell cycle arrest and apoptosis. The anti-apoptotic Bcl-2α protein level was found to be reduced. These findings indicate that DCQ inhibits the growth of ATL cell lines, at least in part, by inducing apoptosis mediated by the modulation of TGF expression, the upregulation in p53 and p21 proteins and downregulation in Bcl-2α expression. The present findings suggest that DCQ merits further investigation as a potential therapeutic agent for this incurable disease. © 2004 Elsevier Ireland Ltd. All rights reserved.
dc.format.extent Pages: (101-113)
dc.language English
dc.publisher CLARE
dc.relation.ispartof Publication Name: Chemico-Biological Interactions; Publication Year: 2004; Volume: 148; no. 3; Pages: (101-113);
dc.source Scopus
dc.title Inhibition of proliferation and induction of apoptosis by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide in adult T-cell leukemia cells
dc.type Article
dc.contributor.affiliation Harakeh, S., Biology Department, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Diab-Assef, M., Biology Department, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation El-Sabban, M., Human Morphology Department, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Haddadin, M., Chemistry Department, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Gali-Muhtasib, H., Biology Department, American University of Beirut, Beirut, Lebanon
dc.contributor.authorAddress Harakeh, S.; Biology Department, American University of Beirut, Beirut, Lebanon; email:
dc.contributor.authorCorporate University: American University of Beirut; Faculty: Faculty of Arts and Sciences; Department: Chemistry;
dc.contributor.authorDepartment Chemistry
dc.contributor.faculty Faculty of Arts and Sciences
dc.contributor.authorInitials Harakeh, S
dc.contributor.authorInitials Diab-Assef, M
dc.contributor.authorInitials El-Sabban, M
dc.contributor.authorInitials Haddadin, M
dc.contributor.authorInitials Gali-Muhtasib, H
dc.contributor.authorReprintAddress Harakeh, S (reprint author), Amer Univ Beirut, Dept Biol, Beirut, Lebanon.
dc.contributor.authorUniversity American University of Beirut
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dc.description.citedCount 14
dc.description.citedTotWOSCount 15
dc.description.citedWOSCount 15
dc.format.extentCount 13
dc.identifier.coden CBINA
dc.identifier.pubmedID 15276867
dc.identifier.scopusID 3342993539
dc.relation.ispartOfISOAbbr Chem.-Biol. Interact.
dc.relation.ispartOfIssue 3
dc.relation.ispartofPubTitle Chemico-Biological Interactions
dc.relation.ispartofPubTitleAbbr Chem.-Biol. Interact.
dc.relation.ispartOfVolume 148
dc.source.ID WOS:000223411600001
dc.type.publication Journal
dc.subject.otherAuthKeyword Antiproliferation
dc.subject.otherAuthKeyword Apoptosis
dc.subject.otherAuthKeyword ATL cells
dc.subject.otherAuthKeyword Bcl-2α
dc.subject.otherAuthKeyword Cell cycle arrest
dc.subject.otherAuthKeyword p53
dc.subject.otherChemCAS protein bcl 2, 219306-68-0
dc.subject.otherChemCAS protein p21, 85306-28-1
dc.subject.otherChemCAS transforming growth factor, 76057-06-2
dc.subject.otherChemCAS 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline-1,4-dioxide
dc.subject.otherChemCAS Quinoxalines
dc.subject.otherIndex 2 benzoyl 3 phenyl 6,7 dichloroquinoxaline 1,4 dioxide
dc.subject.otherIndex antiinfective agent
dc.subject.otherIndex antimitotic agent
dc.subject.otherIndex messenger RNA
dc.subject.otherIndex protein bcl 2
dc.subject.otherIndex protein p21
dc.subject.otherIndex protein p53
dc.subject.otherIndex transforming growth factor
dc.subject.otherIndex transforming growth factor beta1
dc.subject.otherIndex transforming growth factor beta2
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex apoptosis
dc.subject.otherIndex article
dc.subject.otherIndex cell cycle
dc.subject.otherIndex concentration response
dc.subject.otherIndex controlled study
dc.subject.otherIndex down regulation
dc.subject.otherIndex enzyme linked immunosorbent assay
dc.subject.otherIndex female
dc.subject.otherIndex flow cytometry
dc.subject.otherIndex growth inhibition
dc.subject.otherIndex human
dc.subject.otherIndex human cell
dc.subject.otherIndex Human T cell leukemia virus
dc.subject.otherIndex leukemia cell line
dc.subject.otherIndex protein expression
dc.subject.otherIndex T cell leukemia
dc.subject.otherIndex upregulation
dc.subject.otherIndex Adult
dc.subject.otherIndex Apoptosis
dc.subject.otherIndex CD4-Positive T-Lymphocytes
dc.subject.otherIndex Cell Death
dc.subject.otherIndex Cell Division
dc.subject.otherIndex Cell Line, Tumor
dc.subject.otherIndex Cell Survival
dc.subject.otherIndex Dose-Response Relationship, Drug
dc.subject.otherIndex Enzyme-Linked Immunosorbent Assay
dc.subject.otherIndex Female
dc.subject.otherIndex Flow Cytometry
dc.subject.otherIndex Gene Expression Regulation, Neoplastic
dc.subject.otherIndex Human T-lymphotropic virus 1
dc.subject.otherIndex Humans
dc.subject.otherIndex Jurkat Cells
dc.subject.otherIndex Leukemia, Lymphocytic, Acute
dc.subject.otherIndex Leukemia, T-Cell
dc.subject.otherIndex Quinoxalines
dc.subject.otherIndex Human T-lymphotropic virus 1
dc.subject.otherIndex unidentified retrovirus
dc.subject.otherKeywordPlus VIRUS TYPE-I
dc.subject.otherKeywordPlus GROWTH-FACTOR-BETA
dc.subject.otherKeywordPlus NF-KAPPA-B
dc.subject.otherKeywordPlus CREB BINDING-PROTEIN
dc.subject.otherKeywordPlus QUINOXALINE 1,4-DIOXIDES
dc.subject.otherKeywordPlus TRANSACTIVATOR GENE
dc.subject.otherKeywordPlus THERAPEUTIC AGENTS
dc.subject.otherKeywordPlus TRANSFORMED-CELLS
dc.subject.otherKeywordPlus AUTOCRINE LOOP
dc.subject.otherKeywordPlus CYCLE ARREST
dc.subject.otherWOS Biochemistry and Molecular Biology
dc.subject.otherWOS Pharmacology and Pharmacy
dc.subject.otherWOS Toxicology

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