Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells

Klees, Robert F.; De Marco, Paul C.; Salasznyk, Roman M.; Ahuja, Disha; Hogg, Michael; Antoniotti, Sylvain; Kamath, Lakshmi; Dordick, Jonathan S.; Plopper, George E.

doi:https://doi.org/10.1155/JBB/2006/87246

BioMed Research International

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Research Article | Open Access

Volume 2006 | Article ID 087246 | https://doi.org/10.1155/JBB/2006/87246

Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells

Robert F. Klees,¹Paul C. De Marco,¹Roman M. Salasznyk,¹Disha Ahuja,²Michael Hogg,²Sylvain Antoniotti,²Lakshmi Kamath,³Jonathan S. Dordick,²and George E. Plopper¹

Received08 Sept 2005

Accepted13 Oct 2005

Published01 Feb 2006

Abstract

Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics.

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Copyright © 2006 Robert F. Klees 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.

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