Short Communication: Novel Di- and Triselenoesters as Effective Therapeutic Agents Inhibiting Multidrug Resistance Proteins in Breast Cancer Cells

• Published in: International journal of molecular sciences Vol. 25; no. 17; p. 9732
• Main Authors: Radomska, Dominika, Czarnomysy, Robert, Marciniec, Krzysztof, Nowakowska, Justyna, Domínguez-Álvarez, Enrique, Bielawski, Krzysztof
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-09-2024
• Subjects: ABC transporters; anticancer drugs; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily G, Member 2 - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Cell Line, Tumor; Development and progression; Drug resistance; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Drug therapy; Drugs; Esters - chemistry; Esters - pharmacology; Female; Health aspects; Humans; Ligands; MCF-7 Cells; Molecular Docking Simulation; Molecular weight; Mortality; Multidrug Resistance-Associated Proteins - antagonists & inhibitors; Multidrug Resistance-Associated Proteins - metabolism; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - metabolism; organoselenium compounds; Organoselenium Compounds - chemistry; Organoselenium Compounds - pharmacology; Physiological aspects; Prevention; Proteins; Selenium compounds; selenoesters; triple-negative breast cancer; Poland; organoselenium compounds; selenoesters; multidrug resistance; cancer drug resistance; triple-negative breast cancer; molecular docking; selenium compounds; breast cancer; flow cytometry; anticancer drugs
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179732

Breast cancer has the highest incidence rate among all malignancies worldwide. Its high mortality is mainly related to the occurrence of multidrug resistance, which significantly limits therapeutic options. In this regard, there is an urgent need to develop compounds that would overcome this phenomenon. There are few reports in the literature that selenium compounds can modulate the activity of P-glycoprotein (MDR1). Therefore, we performed in silico studies and evaluated the effects of the novel selenoesters EDAG-1 and EDAG-8 on BCRP, MDR1, and MRP1 resistance proteins in MCF-7 and MDA-MB-231 breast cancer cells. The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds-novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy.