title: Modulation of apoptosis protein profiles--role of P-gp in HeLa cells exposed to doxorubicin.
abstract: As shown previously doxorubicin (1 μM) plus sulindac (50 μM) reduced the expression of ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1) mRNA in HeLa cells and this effect was accompanied by increased apoptosis. The aim of this study was to define if the decrease of ABCB1 expression or blocking of P-glycoprotein (P-gp) can affect the expression of the apoptotic genes determined with use of quantitative real time polymerase chain reaction (qRT-PCR). Western blot was used for visualization of chosen pro- and antiapoptotic proteins. Doxorubicin was the main compound which affected the apoptotic genes. The effectiveness of the drugs in reducing of P-gp function has been shown as not being related to the regulation of apoptotic gene transcription. In this experimental scheme, regulation of apoptotic gene transcription depended on the kind of P-gp modulator.
authors.affiliation: Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Chełmska 30/34 Str., 00-725 Warsaw, Poland. b-gruber@il.waw.pl
authors.forename: Beata M
authors.initials: BM
authors.lastname: Gruber
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krzysztoń-Russjan
authors.forename: Irena
authors.initials: I
authors.lastname: Bubko
authors.forename: Mirosława
authors.initials: M
authors.lastname: Koronkiewicz
authors.forename: Elzbieta L
authors.initials: EL
authors.lastname: Anuszewska
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013467:Sulindac / Q000494:pharmacology; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D013467:Sulindac; D004317:Doxorubicin; D014700:Verapamil