Effects of multidrug resistance-related ATP-binding-cassette transporter proteins on the cytoskeletal activity of cytochalasins

Experimental Cell Research
W BergerL Elbling

Abstract

Cytochalasins are microfilament-active mould metabolites, widely utilized to study the involvement of the actin cytoskeleton in cellular processes as well as in genotoxicity and cell kinetic research. In this study we have investigated whether multidrug-resistance phenotypes, caused by overexpression of the ATP-binding-cassette transporter proteins P-glycoprotein (P-gp) or multidrug-resistance-associated protein (MRP), influence the microfilament-depolymerizing effect of cytochalasins. Using four well-characterized multidrug-resistance cell models, we have shown that both the microfilament-disrupting (phalloidine staining) and the cytotoxic (MTT-assay) activity of cytochalasins are reduced in parallel with increased P-gp expression and restorable by P-gp-modulating agents. This also applied to the cytochalasin D-mediated induction of polykaryons (microscopic evaluation) which arise as a consequence of impaired cytokinesis but unaffected karyokinesis. The reduced cellular activity of cytochalasins in P-gp-positive cell lines was correlated with decreased intracellular accumulation ([3H]cytochalasin B accumulation) which was also restorable by P-gp modulators. Moreover, the dose-dependent inhibition of P-gp photoaffinity labeling...Continue Reading

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Citations

Aug 5, 2009·Molecular Nutrition & Food Research·Rita DornetshuberWalter Berger
Oct 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ghulam MurtazaUNKNOWN Mariam
May 11, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiu-Wen WangLi-Wu Fu
Apr 23, 2010·Natural Product Reports·Kirstin ScherlachChristian Hertweck
Dec 3, 2010·Journal of Biomolecular Screening·Vy Lam, Tetsuro Wakatsuki
Sep 21, 2016·Annual Review of Pharmacology and Toxicology·Bruno StiegerWalter Jäger

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