title: Effects of 3β-acethyl tormentic acid (3ATA) on ABCC proteins activity.
abstract: Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors.
authors: Laboratory of Cellular Immunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil.
authors: Gleice
authors: G
authors: Da Graça Rocha
authors: Laboratory of Cellular Immunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil.
authors: Marisol
authors: M
authors: Simões
authors: Department of Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil.
authors: Rodrigo Rodrigues
authors: RR
authors: Oliveira
authors: Department of Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil.
authors: Maria Auxiliadora Coelho
authors: MAC
authors: Kaplan
authors: Laboratory of Cellular Immunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil.
authors: Cerli Rocha
authors: CR
authors: Gattass
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D000882:Haplorhini; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D041681:NIH 3T3 Cells; D014315:Triterpenes / Q000737:chemistry*
chemical_list: D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014315:Triterpenes; C000715087:ABCC2 protein, human; C007695:euscaphic acid; C421109:multidrug resistance-associated protein 1