P-glycoprotein, glutathione and glutathione S-transferase increase in a colon carcinoma cell line by colchicine.
The acquisition of resistance to anticancer agents used in chemotherapy is the main cause of treatment failure in malignant disorders, provoking tumours to become resistant during treatment, although they initially respond to it. The main multidrug resistance (MDR) mechanism in tumour cells is the expression of P-gly-coprotein (P-gly), that acts as an ATP-dependent active efflux pump of chemotherapeutic agents. Furthermore, an increased detoxification of compounds mediated by high levels of glutathione (GSH) and glutathione S-transferase (GST), has been found in resistant cells. We developed a study aiming to evaluate the evolution of the main drug resistance markers in tumour cells: P-gly, GSH and GST, during the acquisition of resistance to colchicine, for the purpose of studying the adaptation process and its contribution to the MDR phenomenon. A human colon adenocarcinoma cell line was exposed to colchicine during 82 days, being P-gly, GSH levels and GST activity evaluated by flow cytometry, spectrofluorimetry and spectrophotometry, during exposure time. P-gly and GSH levels increased gradually during the exposure to colchicine, reaching 2.35 and 3.21 fold each. On day 82, GST activity increased 1.84 fold at the end of the exposure period. Moreover, an increment in drug cross-resistance was obtained that ranges from 2.62 to 5.22 fold for colchicine, vinblastine, vincristine and mitomycin C. The increments obtained in P-gly, GSH and GST could probably contribute to the MDR phenomenon in this human colon adenocarcinoma cell line.
Ruiz-Gómez
M J
MJ
Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Spain.
Souviron
A
A
Martínez-Morillo
M
M
Gil
L
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D016685:Mitomycin; D014750:Vincristine; D014747:Vinblastine; D005982:Glutathione Transferase; D005978:Glutathione; D003078:Colchicine