Lysosomotropic properties of weakly basic anticancer agents promote cancer cell selectivity in vitro.

ABSTRACT: Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity cou

SUBMITTER: Ndolo RA 

PROVIDER: S-EPMC3492287 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature