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Cytotoxic and multidrug resistance reversal activity of phenothiazine derivative is strongly enhanced by theobromine, a phytochemical from cocoa.
Sroda-Pomianek, Kamila; Michalak, Krystyna; Palko-Labuz, Anna; Pola, Andrzej; Dziegiel, Piotr; Pula, Bartosz; Swiatek, Piotr; Wesolowska, Olga.
Afiliación
  • Sroda-Pomianek K; Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland. Electronic address: kamila.sroda-pomianek@umed.wroc.pl.
  • Michalak K; Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland.
  • Palko-Labuz A; Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland.
  • Pola A; Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland.
  • Dziegiel P; Division of Histology and Embryology, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland.
  • Pula B; Division of Histology and Embryology, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland; Department of Hematology, Institute of Hematology and Transfusion Medicine, ul. Gandhi 14, 02-776 Warsaw, Poland.
  • Swiatek P; Department of Drug Chemistry, Wroclaw Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland.
  • Wesolowska O; Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland.
Eur J Pharmacol ; 849: 124-134, 2019 Apr 15.
Article en En | MEDLINE | ID: mdl-30721703
ABSTRACT
The idea of the use of anticancer drugs together with a chemosensitizer emerged as the strategy of reversal of multidrug resistance (MDR) of cancer cells expressing ABC proteins many years ago. The approaches relying on the use of a single chemosensitizer have never resulted in a clinical success. Therefore, the application of drug combinations of two or more compounds with different mechanisms of action might be an alternative approach to increase the success rate. In the present study the cytotoxic and NF-κB inhibition potential of the phenothiazine derivative, MAE-TPR, was evaluated. MAE-TPR was demonstrated to be an effective doxorubicin-resistance modulator in human adenocarcinoma cell line LoVo/Dx. In the presence of MAE-TPR cytotoxicity of doxorubicin was elevated, and its intracellular accumulation increased. Strong synergism occurred between MAE-TPR and Dox. MAE-TPR diminished also the expression of ABCB1 transporter (P-glycoprotein) by affecting NF-κB pathway. Theobromine, a phytochemical from cocoa, which was barely active itself, strongly augmented MDR reversal potency of MAE-TPR. The effect of the combination of phenothiazine derivative with theobromine on cancer cells was studied for the first time in the present work. It was concluded that the use of the proposed combination of two modulators might be a promising strategy for MDR reversal since modulators could be used in concentrations much lower than in case of their single application and in that way the risk of intolerable side-effects could be reduced.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotiazinas / Teobromina / Cacao / Resistencia a Múltiples Medicamentos / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotiazinas / Teobromina / Cacao / Resistencia a Múltiples Medicamentos / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2019 Tipo del documento: Article
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