Sensitivity to microcystins: a comparative study in human cell lines with and without multidrug resistance phenotype.
Multidrug resistance (MDR) is an obstacle in cancer treatment. An understanding of how tumoral cells react to oxidants can help us elucidate the cellular mechanism involved in resistance. Microcystins are cyanobacteria hepatotoxins known to generate oxidative stress. The aim of this study was to compare the sensitivity to microcystins of human tumoral cell lines with (Lucena) and without (K562) MDR phenotype. Endpoints analyzed were effective microcystins concentration to 50% of exposed cells (EC50), antioxidant enzyme activity, lipid peroxidation, DNA damage, reactive oxygen species (ROS) concentration, and tubulin content. Lucena were more resistant and showed lower DNA damage than K562 cells (P<0.05). Although microcystins did not alter catalase activity, a higher mean value was observed in Lucena than in K562 cells. Lucena cells also showed lower ROS concentration and higher tubulin content. The higher metabolism associated with the MDR phenotype should increase ROS concentration and make for an improved antioxidant defense against the toxic effects of microcystins.
de Souza Votto
Ana Paula
AP
Departamento de Ciências Fisiológicas, Fundação Universidade Federal do Rio Grande (FURG), Rio Grande 96201-900, Brazil.
Renon
Viviane Plasse
VP
Yunes
João Sarkis
JS
Rumjanek
Vivian Mary
VM
Marques Capella
Márcia Alves
MA
Neto
Vivaldo Moura
VM
Sampaio de Freitas
Marta
M
Alicia Geracitano
Laura
L
Monserrat
José María
JM
Trindade
Gilma Santos
GS
D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D053858:Metabolic Networks and Pathways; D052998:Microcystins / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D052998:Microcystins; D016877:Oxidants; D017382:Reactive Oxygen Species; D014404:Tubulin