Effects of 3β-acethyl tormentic acid (3ATA) on ABCC proteins activity.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Drug Resistance, Multiple* ; Drug Resistance, Neoplasm*; Multidrug Resistance-Associated Proteins/*metabolism ; Triterpenes/*chemistry; Animals ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Haplorhini ; Humans ; Melanoma, Experimental ; Mice ; Multidrug Resistance-Associated Protein 2 ; NIH 3T3 Cells

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.

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Keywords: 3β-acetyl tormentic acid; ABC transporters; ABCC transporter inhibitor; multidrug resistance; triterpenes
Note: Original DateCompleted: 20130704

0 (ABCC2 protein, human)
0 (Multidrug Resistance-Associated Protein 2)
0 (Multidrug Resistance-Associated Proteins)
0 (Triterpenes)
53155-25-2 (euscaphic acid)
Y49M64GZ4Q (multidrug resistance-associated protein 1)

Date Created: 20120728 Date Completed: 20150908 Latest Revision: 20220922

20231215

PMC3397494

10.3390/ijms13066757

22837662