title: Modulation of ABCC1 and ABCG2 proteins by ouabain in human breast cancer cells.
abstract: ABCC1 and ABCG2 are two transporters associated with multi-drug resistance to cancer chemotherapy. Ouabain is a cardiotonic steroid, currently considered as a hormone associated with arterial hypertension. Previous studies have suggested that ouabain can modulate ABCB1 and ABCC1 expression in cancer and renal cell lines. The present study investigated the effects of physiological concentrations of ouabain on the expression and activity of ABCC1 and ABCG2 in two human breast cancer cell lines, MCF7 and MDA-MB-231, the first known to be responsive to estrogens. Cell viability and proliferation assays showed that 1 μM ouabain reduced proliferation of MCF7, but not if MDA-MB-231 cells. On the other hand, 10 nM ouabain increased proliferation of MDA-MB-231, but not of MCF7 cells. Ouabain (10 nM) prevented the cytotoxic effects of doxorubicin in MCF7 cells, but not in MDA-MB-231 cells. Treatment of cells under different ouabain concentrations for 24 h did not cause any significant effects in the expression of ABCG2 or ABCC1 in either cell line. However, the activity of ABCC1 was increased when MCF7 and MDA-MB-231 cells were treated with 10 mM and 1 nM ouabain respectively. These results claim attention to the possibility that breast cancer patients with high levels of endogenous ouabain may have different responses to chemotherapy.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal d Rio de Janeiro, CCS - Bloco G, 21949-900 Rio de Janeiro, RJ, Brasil. mcapella@biof.ufrj.br.
authors.forename: Vanessa Amil
authors.initials: VA
authors.lastname: DA Silva
authors.forename: Karla Andreza Elizeu Pereira
authors.initials: KA
authors.lastname: DA Silva
authors.forename: João Marcos Azevedo
authors.initials: JM
authors.lastname: Delou
authors.forename: Leonardo Marques
authors.initials: LM
authors.lastname: DA Fonseca
authors.forename: Anibal Gil
authors.initials: AG
authors.lastname: Lopes
authors.forename: Márcia Alves Marques
authors.initials: MA
authors.lastname: Capella
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D010042:Ouabain; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABCB1; ABCC1; MCF7; MDA-MB-231 cells; Ouabain