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Drug Metabolism Letters


ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

P-Glycoprotein Is Not a Key Target for the Chemosensitizing Effect of 1-Phenyl-2-Decanoylamino-3-Morpholino-1-Propanol in HepG2 Cells Exposed to Doxorubicin

Author(s): Sabrina Di Bartolomeo, Paolo Luly and Angelo Spinedi

Volume 4, Issue 1, 2010

Page: [39 - 44] Pages: 6

DOI: 10.2174/187231210790980471

Price: $65


Chemosensitization of HepG2 cells to doxorubicin by 1-phenyl-2-decanoylamino-3-morpholino-1-propanol neither impinged on downregulation of P-glycoprotein expression nor on severe impairment of its activity. Moreover, differently from verapamil, a potent P-glycoprotein inhibitor, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol chemosensitized HepG2 cells in a fashion that was insensitive to the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Aspfluoromethylketone. At concentrations exceeding the one employed for chemosensitization, 1-phenyl-2-decanoylamino-3- morpholino-1-propanol was by itself strongly toxic to HepG2 cells, and also this effect was insensitive to the pancaspase inhibitor. These results suggest that 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, at subtoxic concentrations, might synergize with scarcely toxic doxorubicin doses to propagate a caspase-independent cytotoxic response, such that P-glycoprotein-dependent drug resistance is circumvented.

Keywords: Drug resistance, P-glycoprotein, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, verapamil, doxorubicin, HepG2 cells

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