Novel caffeic acid ester derivative induces apoptosis by expressing FasL and downregulating NF-KappaB: Potentiation of cell death mediated by chemotherapeutic agents.
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.
Bose
Julie S
JS
Reliance Life Sciences Pvt. Ltd., Mumbai, India.
Gangan
Vijay
V
Jain
Swatantra K
SK
Manna
Sunil K
SK
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
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