title: Synergy of BID with doxorubicin in the killing of cancer cells.
abstract: Overexpression of the BH3-interacting domain death agonist (BID) protein sensitizes certain cancer cell lines to apoptosis induced by anticancer agents, particularly by those acting through death receptors (e.g. TRAIL). Previously, we showed that recombinant BID fused with TAT cell penetrating peptide (TAT-BID) allowed for controlled delivery of BID to different cancer cell lines and moderately sensitized some of them to TRAIL or slightly to camptothecin. In the present study, we showed that TAT-BID delivered to HeLa cells strongly sensitized them to doxorubicin, as identified by cell viability and apoptosis assays. Another cell line sensitized to doxorubicin was PC3, whereas A549 and LNCaP cells were sensitized moderately or not at all, respectively. Sensitization was more pronounced at 1 µM doxorubicin administered for 48 h than for lower doses and shorter treatments. TAT-BID and doxorubicin may thus be considered as a potential therapeutic combination for cervical carcinoma and advanced prostate cancer treatment.
authors.affiliation: Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
authors.forename: Emilia Joanna
authors.initials: EJ
authors.lastname: Orzechowska
authors.affiliation: Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Girstun
authors.affiliation: Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Staron
authors.affiliation: Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trzcinska-Danielewicz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000008:administration & dosage*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D015696:Gene Products, tat; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D015696:Gene Products, tat; D011994:Recombinant Proteins; D004317:Doxorubicin