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-kappa B) activation and NF-kappa B-dependent genes expression. CAMVE-mediated inhibition of NF-kappa B or induction of cell death is not cell type specific. CAMVE inhibits cell proliferation by inhibiting GI 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-kappa B 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.