Cytotoxic effect induced by combination of polyamines metabolites and endocannabinoid, anandamide, on human cancer cells: a new anticancer strategy

Abstract

Polyamines are necessary for cell proliferation and are detected at higher concentrations in most tumor tissues. Bovine serum amine oxidase (BSAO) can generate in situ cytotoxic products such as H2O2 and aldehydes from oxidation of polyamines, as a new approach in cancer therapy [1]. The present results show that multidrug-resistant human colon adenocarcinoma cells (LoVo) are significantly more sensitive than corresponding wild-type cells to the cytotoxic products. Pre-treatment of the cells with anandamide (AEA) (Figure ​(Figure1),1), an endocannabinoid which effect can be either central, in the brain, mediated by CB1 receptors, or peripheral in other organs and tissues where CB2 receptors are expressed, sensitized both cell lines to the subsequent exposure to spermine metabolites amplifying the ability of these products to induce cell death [2]. Figure 1 The sensitizing effect was also greater on multidrug-resistant cells than wild-type ones, an aspect of particular importance since conventional cancer therapy suffers from the development of drug resistance. Cell viability was determined using MTT assay [3]. Concentrations 0-100 µM of AEA were tested, for incubation times up to 24 h; and concentrations 0-8 µM of spermine in presence of BSAO were used, for incubation times up to 1 h.