title: Novel caffeic acid ester derivative induces apoptosis by expressing FasL and downregulating NF-KappaB: Potentiation of cell death mediated by chemotherapeutic agents.
abstract: In the present study, we demonstrate the biological activity of esterified caffeic acid with methyl vanillate also termed as caffeic acid methyl vanillate ester (CAMVE). CAMVE potentiates TNF-induced cell death as analyzed by cell viability assay and blocks inflammatory stimuli-induced nuclear transcription factor kappaB (NF-kappaB) activation and NF-kappaB-dependent genes expression. CAMVE-mediated inhibition of NF-kappaB or induction of cell death is not cell type specific. CAMVE inhibits cell proliferation by inhibiting G1 to S phase progression. It suppresses TNF-induced Bcl-2 expression and potentiates chemotherapeutic agents-mediated cell death. CAMVE enhances intracellular free Ca(2+) and thereby activates calcineurin. Calcineurin, in turns, activates nuclear transcription factor NF-AT and its dependent genes such as FasL, which induces cell death. The data demonstrate that CAMVE is one of the combinatorial products, which is able to inhibit NF-kappaB regulated genes and cell proliferation. The combinatorial synthesis of novel caffeic ester derivatives can be a useful approach to generate potent chemotherapeutic agents and designing CAMVE as potent therapeutic agent for combination therapy may be useful to treat tumors.
authors.affiliation: Reliance Life Sciences Pvt. Ltd., Mumbai, India.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Bose
authors.forename: Vijay
authors.initials: V
authors.lastname: Gangan
authors.forename: Swatantra K
authors.initials: SK
authors.lastname: Jain
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Manna
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004357:Drug Synergism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002109:Caffeic Acids; C491901:FAS protein, human; D053222:Fas Ligand Protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D004533:Egtazic Acid; D004247:DNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051550:I-kappa B Kinase; D019703:Calcineurin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C497945:caffeic acid methyl ester; D002118:Calcium