tosylphenylalanyl-chloromethyl-ketone and Ovarian-Neoplasms

TNF is one of the key cytokines involved in cancer development. TNF signaling can result in both stimulating and inhibitory signals that can result in opposite biological effects in cancerogenesis. 2-(1-adamantylamino)-6-methylpyridine (AdAMP) enhances TNF secretion whereas N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) is a NF-κB inhibitor potentially stimulating proapoptotic TNF signals. The aim of the study was to assess the effect of TPCK in combination with AdAMP on human ovarian cells.. CAOV-1 human ovarian cell line was incubated with TPCK and AdAMP for 24 hours. The cytotoxic effect was evaluated in a crystal violet assay. A monoclonal antibody against TNF, Infliximab, was added to examine the possible mechanism of interactions.. Depending on concentration, AdAMP potentialized cytotoxic activity of TPCK or had a synergistic effect with TPCK. Infliximab did not reverse cytotoxicity of AdAMP and TPCK and in some cytotoxic and non-cytotoxic concentrations even enhanced their cytotoxicity.. AdAMP and TPCK cytotoxicity seems to be dependent on TNF signaling, however, the exact mechanism of interactions remains unclear.

Topics: Adamantane; Aminopyridines; Apoptosis; Cell Line, Tumor; Cell Survival; Drug Synergism; Female; Humans; Infliximab; Ovarian Neoplasms; Signal Transduction; Tosylphenylalanyl Chloromethyl Ketone; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha