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Cyclophosphamide Metabolite Inducing Apoptosis in RLS Mouse Lymphosarcoma Cells Is a Substrate for P-Glycoprotein.


Bull Exp Biol Med. 2012 Jan;152(3):348-52


Authors: Patutina OA, Mironova NL, Logashenko EB, Popova NA, Nikolin VP, Vasil'ev GV, Kaledin VI, Zenkova MA, Vlasov VV


Abstract

RLS lymphosarcoma characterized by enhanced expression of mdr1a and mdr1b genes encoding P-glycoprotein is insensitive to low doses of cyclophosphamide, but is susceptible to its high doses approximating the maximum tolerated doses. Induction of apoptotic death of RLS cells by high doses of cyclophosphamide was demonstrated by cytofluorometry and electrophoresis. Experiments on RLS(40) tumor cells derived from RLS lymphosarcoma and characterized by more intensive expression of mdr1a/1b genes showed that the therapeutic effects of cyclophosphamide increased under conditions of simultaneous suppression of these genes by specific small interfering RNA (siRNA). These findings suggest that active cyclophosphamide metabolite can be a substrate for P-glycoprotein.

PMID: 22803083 [PubMed - in process]