A novel mechanism of drug resistance to an anticancer drug, Temoxifen unveiled through interference with iron homeostasis

Bhawna Nishal, Anil K. Sharma, Raman Kumar, Vikas Beniwal, Sardul S. Sandhu

Abstract


Many drug resistance mechanisms have been known in organisms attributed to many factors such as reduced drug accumulation, reduced amount taken up by the cells, cellular excretion, enhanced detoxification mechanisms, inhibition of apoptotic signals, altered drug metabolism, enhanced DNA repair and altered drug target etc. The present investigations have been carried out to delineate another possible mechanism of drug resistance as iron m i g h t i n t e r f e r e w i t h a n t i c a n c e r d r u g , Temoxifen.Temoxifen was introduced into the yeast, Saccharomyces cerevisiae OCY356 strain having Fet3LacZ on the chromosome. Temoxifen not only resulted in decreased growth but also found to chelate iron to some extent which resulted in increased levels of Aft-1 regulated gene expression. Therefore iron levels in the cell may interfere with the drug, Temoxifen pointing towards a novel mechanism of drug resistance.


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