Mitochondrial alterations induced by serum amine oxidase and spermine on human multidrug resistant tumor cells

Amino Acids
G AranciaE Agostinelli

Abstract

Multidrug resistance (MDR) has been studied extensively because it is one of major problems in cancer chemotherapy. The MDR phenotype is often due to overexpression of P-glycoprotein (P-gp), that acting as an energy-dependent drug efflux pump exports various anticancer drugs out of cells. The major goal of our investigation is to establish whether bovine serum amine oxidase (BSAO), which generates the products H(2)O(2) and aldehyde(s), from the polyamine spermine, is able to overcome MDR of human cancer cells. The cytotoxicity of the products was evaluated in both drug-sensitive (LoVo WT) and drug-resistant (LoVo DX) colon adenocarcinoma cells. A clonogenic cell survival assay demonstrated that LoVo DX cells were more sensitive than LoVo WT cells. Exogenous catalase protected cells against cytotoxicity mainly due to the formation of H(2)O(2). However, spermine-derived aldehyde(s) still induced some cytotoxicity. The cytotoxic effect was totally inhibited in the presence of both enzymes, catalase and NAD-dependent aldehyde dehydrogenase (ALDH). Transmission electron microscopy investigations showed that BSAO and spermine induced evident mitochondria alterations, more pronounced in MDR than in LoVo WT cells. The mitochondrial act...Continue Reading

Citations

Sep 10, 2005·Apoptosis : an International Journal on Programmed Cell Death·M SchillerH M Lorenz
Oct 18, 2005·Biochimica Et Biophysica Acta·Antonio ToninelloBruno Mondovì
Oct 20, 2018·The Journal of Biological Chemistry·Tracy Murray StewartRobert A Casero
Nov 15, 2011·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Seiji IsonishiTadao Tanaka
Sep 30, 2016·Amino Acids·Enzo Agostinelli

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