Characterization of multidrug resistance in SEWA mouse tumor cells: increased glutathione transferase activity and reversal of resistance with verapamil.
The glutathione transferase (EC 2.5.1.18) activity of multidrug-resistant and drug-sensitive SEWA mouse tumor cells was determined. Increase in activity was found in all multidrug-resistant sublines. Electrophoretic separation of cytosolic proteins and immunodetection, using antisera against Class Alpha, Class Mu and Class Pi glutathione transferase, revealed a two-fold increase of the Class Pi transferase in the resistant cells. The role of glutathione transferase of Class Pi in the multidrug resistance and its distinction from the over-produced 21,000 dalton protein p21 is discussed. Reversal of the resistance, using the calcium antagonist verapamil, and different sensitivity to verapamil between different sublines are also reported.
D000818:Animals; D002460:Cell Line; D004351:Drug Resistance / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology; D014700:Verapamil / Q000494:pharmacology*
D009363:Neoplasm Proteins; D014700:Verapamil; D005982:Glutathione Transferase