Chalcones, potential anticancer agents, have shown promise in the suppression of multidrug resistance due to the inhibition of drug efflux driven by certain adenosine triphosphate (ATP)-binding cassette (ABC) transporters. The gene and protein expression of chosen ABC transporters (multidrug resistance protein 1, ABCB1; multidrug resistance-associated protein 1, ABCC1; and breast cancer resistance protein, ABCG2) in human colorectal cancer cells (COLO 205 and COLO 320, which overexpress active ABCB1) was mainly studied in this work under the influence of a novel synthetic acridine-based chalcone, 1C. While gene expression dropped just at 24 h, compound 1C selectively suppressed colorectal cancer cell growth and greatly lowered ABCB1 protein levels in COLO 320 cells at 24, 48, and 72 h. It also reduced ABCC1 protein levels after 48 h. Molecular docking and ATPase tests show that 1C probably acts as an allosteric modulator of ABCB1. It also lowered galectin-1 (GAL1) expression in COLO 205 cells at 24 h. Functional tests on COLO cells revealed ABCB1 and ABCC1/2 to be major contributors to multidrug resistance in both. Overall, 1C transiently lowered GAL1 in COLO 205 while affecting important functional ABC transporters, mostly ABCB1 and to a lesser extent ABCC1 in COLO 320 cells. COLO 320's absence of GAL1 expression points to a possible yet unknown interaction between GAL1 and ABCB1.

• Keywords
• ABCB1, ABCC1, ABCG2, chalcone, colorectal carcinoma, drug efflux, expression, galectin-1, multidrug resistance, transporter,
• MeSH
• ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism   MeSH
• ATP-Binding Cassette Transporters * metabolism   chemistry   genetics   MeSH
• Acridines * chemistry   pharmacology   MeSH
• Chalcone * pharmacology   chemistry   MeSH
• Chalcones * pharmacology   chemistry   MeSH
• Drug Resistance, Neoplasm drug effects   MeSH
• Colorectal Neoplasms metabolism   drug therapy   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• ATP Binding Cassette Transporter, Subfamily B metabolism   genetics   MeSH
• Cell Proliferation drug effects   MeSH
• Multidrug Resistance-Associated Protein 2 MeSH
• Multidrug Resistance-Associated Proteins metabolism   genetics   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Molecular Docking Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
• ATP-Binding Cassette Transporters * MeSH
• ABCB1 protein, human MeSH Browser
• ABCC2 protein, human MeSH Browser
• Acridines * MeSH
• Chalcone * MeSH
• Chalcones * MeSH
• multidrug resistance-associated protein 1 MeSH Browser
• ATP Binding Cassette Transporter, Subfamily B MeSH
• Multidrug Resistance-Associated Protein 2 MeSH
• Multidrug Resistance-Associated Proteins MeSH
• Antineoplastic Agents * MeSH