An analysis of the effect of thioacetazone on P-glycoprotein activity

 

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Taylor CĀ Jaicks
Committee: Dana Emmert, Jeff Holmes, Langdon Martin

In the effort to combat the rising number of multiple drug resistant strains of tuberculosis in the global population, it is critical to study membrane transport proteins responsible for resistance in other disease treatments. Results of these studies have major implications in drug design, tuberculosis testing, and treatment regimens for infected patients. In order to study interactions between the antitubercular drug, thiacetazone, and P-glycoprotein, an ATP-binding cassette protein responsible for multiple drug resistance in cancer and malaria treatment, MCF-7 cells and DX-1 p-gp overexpressing cells were cultured and tested for thiacetazone interaction. Cell viability and substrate accumulation assays were used to measure drug toxicity in cells and effect on p-gp, respectively. Mean absorbance and fluorescence were subjected to one-way analysis of variance testing for significance. Findings suggest therapeutic doses of thiacetazone are non-toxic to cells, and do not inhibit substrate efflux by p-gp. This indicates that anti-resistance properties of thiacetazone are not due to inhibition of p-glycoprotein, but rather, inhibition of another biological mechanism. Further research is indicated in testing other antitubercular agents on efflux proteins to increase or knowledge in this area.