Reversal of Multidrug Resistance in Murine Lymphoma Cells by Amphiphilic Dihydropyridine Antioxidant Derivative

• Published in: Anticancer research Vol. 30; no. 10; pp. 4063 - 4069
• Main Authors: CINDRIC, Marina, CIPAK, Ana, ZARKOVIC, Neven, MOLNAR, József, SERLY, Julianna, PLOTNIECE, Aiva, JAGANJAC, Morana, MRAKOVCIC, Lidija, LOVAKOVIC, Tomislava, DEDIC, Azra, SOLDO, Ivo, DUBURS, Gunars
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.10.2010
• Subjects: Animals; Antioxidants - pharmacology; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biological and medical sciences; Dihydropyridines - pharmacology; Doxorubicin - pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Hematologic and hematopoietic diseases; Humans; Leukemia L5178; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - metabolism; Medical sciences; Mice; Reactive Oxygen Species - metabolism; Transfection; Tumors; Antineoplastic agent; Oxidative stress; Doxorubicin; MDR reversal; Isomerases; Cancerology; Lymphoproliferative syndrome; Multiple resistance; Dihydropyridine derivatives; DNA topoisomerase (ATP-hydrolysing); Treatment resistance; Enzyme; Rodentia; Enzyme inhibitor; Malignant hemopathy; Topoisomerase II inhibitor; Malignant tumor; Lymphoid neoplasm; Antioxidant; Lymphoma; Vertebrata; Mammalia; Mouse; Animal; Reversibility; dihydropyridine derivative; Anthracyclins; Cancer
• ISSN: 0250-7005; 1791-7530

Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies. The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance. The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1-expressing mouse lymphoma cells and their parental control. The effects of K-2-11 with and without doxorubicin were studied by determination of cell viability, cell proliferation and production of reactive oxygen species. K-2-11 caused complete reversal of multidrug resistance of the MDR cells, being much more efficient than the positive control verapamil. Accordingly, the cytotoxic effects of doxorubicin were enhanced by K-2-11, both in the MDR and in parental cell line, while K-2-11 alone did not affect cell viability. K-2-11 also acted as an antioxidant, reducing the cellular generation of reactive oxygen species. Our results indicate the high potential of K-2-11 as a novel antioxidant with potent MDR-blocking ability that should be studied further for development in adjuvant anticancer treatments.