title: Carboplatin and sodium butyrate, separate--yes, but combined--never.
abstract: With the object of improving the effectiveness of a malignant melanoma's treatment and a patients' quality of life, there is a serious need to identify new anticancer compounds, for example, among naturally derived compounds such as sodium butyrate. The aim of this study was to assess the combined impact of carboplatin (C) and sodium butyrate on the B16 melanoma viability by in vitro. B16 cell line was exposed to various concentrations of carboplatin (0.001-10 micromol/L) and sodium butyrate (1 to 100 mmol/L) for 24 h. LC10, LC50 and LC90 values were calculated. The influence of carboplatin and sodium butyrate on the cell cycle and apoptosis was assessed. Additionally, magnetic stem cell sorting was performed, positive melanoma CD133 cells were isolated and the effects of carboplatin and sodium butyrate on cell viability with heterogeneous population of melanoma cells (CD133+/CD133-) was compared. For carboplatin LC50 and LC90 were 1.2 micromol/L and 4.58 pmol/L, respectively. For sodium butyrate LC50 and LC90 were 65.73 mmol/L and 275.06 mmol/L. The value for LC10 could not be determined. Sodium butyrate at the highest concentration (100.0 mmol/L) resulted in only 57.36% mortality of cells. A synergistic effect of both compounds was observed in low concentrations of sodium butyrate and carboplatin. That synergism disappeared at concentrations corresponding to LC50. At the concentration corresponding to LC50 C and high concentration of sodium butyrate, a decrease of cell numbers in phase G2/M was observed (r = -0.97). Cells were arrested in phase G1/G0 and S. The presented results exclude the possibility of the combined application of sodium butyrate and carboplatin in cancer therapy.
authors.affiliation: Department of Tissue Engineering, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Karłowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gurtowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kloskowski
authors.forename: Joanna
authors.initials: J
authors.lastname: Olkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Bajek
authors.forename: Robert
authors.initials: R
authors.lastname: Debski
authors.forename: Jowita
authors.initials: J
authors.lastname: Zielaskowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Drewa
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006023:Glycoproteins / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D018189:Immunomagnetic Separation; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002087:Butyrates; D006023:Glycoproteins; D056572:Histone Deacetylase Inhibitors; D010455:Peptides; C000606024:Prom1 protein, mouse; D016190:Carboplatin