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Ketone-selenoesters as potential anticancer and multidrug resistance modulation agents in 2D and 3D ovarian and breast cancer in vitro models.
Dobiasová, Simona; Szemerédi, Nikoletta; Kucerová, Denisa; Koucká, Kamila; Václavíková, Radka; Gbelcová, Helena; Ruml, Tomás; Domínguez-Álvarez, Enrique; Spengler, Gabriella; Viktorová, Jitka.
Afiliación
  • Dobiasová S; Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 3, 166 28, Prague 6, Czechia.
  • Szemerédi N; Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, Szeged, 6725, Hungary.
  • Kucerová D; Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 3, 166 28, Prague 6, Czechia.
  • Koucká K; Toxicogenomics Unit, National Institute of Public Health, Srobárova 49, 100 00, Prague, Czechia.
  • Václavíková R; Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 323 00, Pilsen, Czechia.
  • Gbelcová H; Toxicogenomics Unit, National Institute of Public Health, Srobárova 49, 100 00, Prague, Czechia.
  • Ruml T; Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 323 00, Pilsen, Czechia.
  • Domínguez-Álvarez E; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 4, 811 08, Bratislava, Slovakia.
  • Spengler G; Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 3, 166 28, Prague 6, Czechia.
  • Viktorová J; Instituto de Química Orgánica General (IQOG-CSIC), Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, 28006, Madrid, Spain. e.dominguez-alvarez@iqog.csic.es.
Sci Rep ; 12(1): 6548, 2022 04 21.
Article en En | MEDLINE | ID: mdl-35449387
ABSTRACT
Long-term treatment of cancer with chemotherapeutics leads to the development of resistant forms that reduce treatment options. The main associated mechanism is the overexpression of transport proteins, particularly P-glycoprotein (P-gp, ABCB1). In this study, we have tested the anticancer and multidrug resistance (MDR) modulation activity of 15 selenocompounds. Out of the tested compounds, K3, K4, and K7 achieved the highest sensitization rate in ovarian carcinoma cells (HOC/ADR) that are resistant to the action of the Adriamycin. These compounds induced oxidation stress, inhibited P-gp transport activity and altered ABC gene expression. To verify the effect of compounds, 3D cell models were used to better mimic in vivo conditions. K4 and K7 triggered the most significant ROS release. All selected selenoesters inhibited P-gp efflux in a dose-dependent manner while simultaneously altering the expression of the ABC genes, especially P-gp in paclitaxel-resistant breast carcinoma cells (MCF-7/PAX). K4, and K7 demonstrated sensitization potential in resistant ovarian spheroids. Additionally, all selected selenoesters achieved a high cytotoxic effect in 3D breast and ovarian models, which was comparable to that in 2D cultures. K7 was the only non-competitive P-gp inhibitor, and therefore appears to have considerable potential for the treatment of drug-resistant cancer.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Antineoplásicos Límite: Female / Humans Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Antineoplásicos Límite: Female / Humans Idioma: En Año: 2022 Tipo del documento: Article