Table of Contents
ISRN Pharmacology
Volume 2012 (2012), Article ID 307102, 10 pages
http://dx.doi.org/10.5402/2012/307102
Research Article

Menadione : Sodium Orthovanadate Combination Eliminates and Inhibits Migration of Detached Cancer Cells

1Department of Clinical Neuroscience, Karolinska Institute, Karolinska University Hospital, 141 86 Stockholm, Sweden
2Brain Research Centre, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
3Department of Neurology, Karolinska University Hospital, 141 86 Stockholm, Sweden

Received 25 April 2012; Accepted 5 July 2012

Academic Editors: J. C. Clapham, G. Edwards, R. Fantozzi, and S. Kitayama

Copyright © 2012 Zahid M. Delwar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment. In addition, we followed the fate and chemosensitivity of M : SO-induced detached cells. Using transwell chambers, we found that a fraction of the M : SO-induced detached cells were viable and, furthermore, were able to migrate, re-attach, and resume proliferation when re-incubated in drug-free media. The total elimination of A549 detachment-resistant cells and M : SO-induced detached cells were successfully eliminated by equivalent M : SO concentration (17.5 μM : 17.5 μM). Thus, M : SO prevented cell migration. Similar results were obtained on DBTRG.05MG human glioma cells. Our data guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their implications for invasiveness and metastasis and their sensitivity to anticancer drugs.