This article is part of the supplement: Abstracts of the 16th International Charles Heidelberger Symposium on Cancer Research

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Delocalized lipophilic cations as a new therapeutic approach in cancer

A Barbosa Ribeiro1*, A Luísa Ferreira1, A Cristina Gonçalves12, Sílvia Neves23, A Maria Araújo1, Filipa Carvalho1, João Carvalho1, Rui M Santos1, Vera Alves1, Teresa Silva1, José M Nascimento-Costa245 and Ana B Sarmento-Ribeiro123

Author Affiliations

1 Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal

2 Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal

3 Center for Neuroscience and Cell Biology, Coimbra, Portugal

4 Medicine Service and Hepatology Unity, University Hospital of Coimbra, Coimbra, Portugal

5 University Hematology Clinic, FMUC, Coimbra, Portugal

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BMC Proceedings 2010, 4(Suppl 2):P30  doi:10.1186/1753-6561-4-S2-P30

The electronic version of this article is the complete one and can be found online at:

Published:24 September 2010

© 2010 Ribeiro et al; licensee BioMed Central Ltd.

Poster presentation

Delocalized lipophilic cations (DLCs) penetrate plasma and mitochondrial membranes and accumulate in mitochondria. The higher mitochondrial membrane potentials of neoplastic vs normal cells, in general, account for greater uptake and may be a way to selectively target these cells since. Dequalinium (DQA) is a DLC and so our goal is to evaluate the therapeutic potential of DQA in cancer, namely in B-cell Chronic Lymphocytic Leukaemia (B-CLL), Acute Promyelocytic Leukaemia (APL) and Hepatocellular Carcinoma (HCC).

For this we used 3 cell lines, EHEB (B-CLL), HL-60 (APL) and HUH-7 (HCC), to evaluate the effect of different concentrations of DQA either by single dose administration, by daily dose administration and by association with conventional anticarcinogenic agents. Cell viability and death was determined by the resazurin assay, optical microscopy and by flow cytometry. The latter was also used to evaluate the mitochondrial membrane potential, the levels of ROS (H2O2; O2•-) and the antioxidant defense, Reduced Glutathione (GSH), using fluorescent probes.

We found that DQA induced a decrease in cell viability inducing cell death by late apoptosis/necrosis in a time, dose and cell type dependent manner, with and IC50 of 2.5, 4.7 and 7.5 μM at 48h of exposure, respectively to HL-60, HUH-7 and EHEB. These effects may be mediated by oxidative stress as we have observed and increase in ROS production and a decrease in GSH levels and in mitochondrial membrane potential. We also observed that if DQA is administered on a daily basis a much lower concentration is required to induce the same effect. On the other hand, the association of DQA with the conventional drug induces a synergistic effect, because lower concentration of both drugs is required to obtain the some effect.