Additive Interaction of Cisplatin and Histone Deacetylase Inhibitors Combined Treatment in Rhabdomyosarcoma Cells - An Isobolographic Analysis.
The aim of this study was to assess the anticancer effect and the type of pharmacologic drug-drug interaction of cisplatin (CDDP) and histone deacetylase inhibitors (HDIs) combined treatment on the rhabdomyosarcoma cell line.



The antiproliferative actions of cisplatin and suberoylanilide hydroxamic acid (SAHA, vorinostat), as well as valproic acid (VPA) alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay and isobolographic analysis.



All tested compounds inhibited proliferation of rhabdomyosarcoma cancer cells in a dose-dependent manner. The combinations of CDDP with SAHA and CDDP with VPA produced additive interaction with type-I isobolographic analysis.



When adding SAHA or VPA to CDDP therapy, one can expect additive anticancer effects in the rhabdomyosarcoma cell line.
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Agata
A
Jarząb
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Jarogniew J
JJ
Łuszczki
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Małgorzata
M
Guz
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Ewelina
E
Gumbarewicz
Department of Otolaryngology, MSWiA Hospital, Lublin, Poland.
Krzysztof
K
Polberg
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland andrzej.stepulak@umlub.pl.
Andrzej
A
Stepulak
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D012208:Rhabdomyosarcoma / Q000473:pathology*; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000077337:Vorinostat
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D014635:Valproic Acid; D002945:Cisplatin
Rhabdomyosarcoma; SAHA; VPA; cisplatin; histone deacetylase inhibitors; isobolographic analysis