Effects of Multidrug Resistance-Related ATP-Binding-Cassette Transporter Proteins on the Cytoskeletal Activity of Cytochalasins

摘要: Abstract Cytochalasins are microfilament-active mould metabolites, widely utilized to study the involvement of actin cytoskeleton in cellular processes as well genotoxicity and cell kinetic research. In this we have investigated whether multidrug-resistance phenotypes, caused by overexpression ATP-binding-cassette transporter proteins P-glycoprotein (P-gp) or multidrug-resistance-associated protein (MRP), influence microfilament-depolymerizing effect cytochalasins. Using four well-characterized models, shown that both microfilament-disrupting (phalloidine staining) cytotoxic (MTT-assay) activity cytochalasins reduced parallel with increased P-gp expression restorable P-gp-modulating agents. This also applied cytochalasin D-mediated induction polykaryons (microscopic evaluation) which arise a consequence impaired cytokinesis but unaffected karyokinesis. The P-gp-positive lines was correlated decreased intracellular accumulation ([ 3 H]cytochalasin B accumulation) modulators. Moreover, dose-dependent inhibition photoaffinity labeling H]azidopine) suggested P-gp-binding contrast, MRP had no on either microfilament cytotoxicity. conclusion, data indicate microfilament-destructive effects due reduction not MRP. Results discussed regard resistance factor when dynamics, cycle kinetics chromosomal damage. polykaryon-inducing D is specific indicator for P-gp-mediated phenotype reversing potency chemosensitizers.