Oleanolic acid inhibits the activity of the multidrug resistance protein ABCC1 (MRP1) but not of the ABCB1 (P-glycoprotein): possible use in cancer chemotherapy.
The effects of oleanolic acid (OA) on ABCB1 and ABCC1 activities were studied in a cell line constitutively expressing both proteins. It was observed that OA did not alter ABCB1 activity, but inhibited the activity of ABCC1 protein. This inhibition was reversible and only occurred in the presence of OA. In addition, OA did not alter the expression of ABCC1 mRNA. These results suggest that OA could be a good choice in the treatment of MDR tumours, either as a chemotherapic itself in tumours bearing ABCB1, or as an adjuvant in the chemotherapy of ABCC1 expressing tumours.
Braga
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F
Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Ayres-Saraiva
D
D
Gattass
C R
CR
Capella
M A M
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009828:Oleanolic Acid; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1