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One of the most promising strategies in colon cancer therapy is the sensitization of cancer cells to natural proapoptotic cytokines, such as death ligands and interferons, which are able to eliminate abnormal cells. The investigation of mechanisms determining the immune escape of cancer cells revealed the presence of antiapoptotic proteins, such as cFLIP, which inhibit cell death signal transduction. Numerous studies showed that the use of different metabolic inhibitors, such as cycloheximide (CHX), reduces the cFLIP protein level, thus restoring the susceptibility to TNF-a-induced apoptosis. However, high non-specific toxicity of CHX excludes the clinical use of this substance. The current efforts are focused on identification of bioactive compounds which could safely support immunotherapy. The review presents in vitro and in vivo evidence that butyrate (Bt), fatty acid produced in colon during fermentation process and parthenolide (PN), sesquiterpene lactone isolated from Tanacetum parthenium specifically affect different cancer cells. Among described various molecular mechanisms of Bt and PN action, one reduces the level of antiapoptotic proteins. This paper clearly demonstrates that bioactive compounds, especially combined with immune cytokines could be seriously considered as an alternative for routine colon anti-cancer therapy.
Gut-derived adenocarcinoma Caco-2 cells were treated with sodium butyrate (NaB) at physiologically relevant concentrations. We characterized its effects on prolifera­tion, differentiation, apoptosis, adhesion to the solid support and interleukin-8 secre­tion. Differentiation was determined by brush border alkaline phosphatase activity. Apoptosis was assessed by acridine orange and Hoechst stains. Differentiation and apoptosis were analyzed in both adherent and floating cell populations. The trans­formed Caco-2 cells did not retain their malignant phenotype in the presence of NaB. They appeared to undergo a change in the phenotype induced by NaB, as indicated by reduced proliferation, enhanced differentiation, stimulation of apoptosis leading to decreased viability of cells, and stimulation of interleukin-8 secretion. Considering all the above facts and data, we postulate that Caco-2 cells cultured in NaB supplemented medium could regain the phenotypic characteristics of the phenotype of the parent cell from which originated the Caco-2 line.
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