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Mol. Cells 2012; 33(4): 363-369

Published online April 30, 2012

https://doi.org/10.1007/s10059-012-2285-2

© The Korean Society for Molecular and Cellular Biology

Antioxidant Dieckol Downregulates the Rac1/ROS Signaling Pathway and Inhibits Wiskott-Aldrich Syndrome Protein (WASP)-Family Verprolin-Homologous Protein 2 (WAVE2)-Mediated Invasive Migration of B16 Mouse Melanoma Cells

Sun Joo Park*, Yong Tae Kim1, and You Jin Jeon2

Department of Chemistry, Pukyong National University, Busan 608-737, Korea, 1Department of Food Science and Biotechnology, Kunsan National University, Kunsan 573-701, Korea, 2Department of Marine Life Science, Jeju National University, Jeju 690-756, Korea

Correspondence to : *Correspondence: parksj@pknu.ac.kr

Received: December 20, 2011; Revised: February 7, 2012; Accepted: February 17, 2012

Abstract

Reactive oxygen species (ROS) generation is linked to dynamic actin cytoskeleton reorganization, which is in-volved in tumor cell motility and metastasis. Thus, inhibi-tion of ROS generation and actin polymerization in tumor cells may represent an effective anticancer strategy. However, the molecular basis of this signaling pathway is currently unknown. Here, we show that the Ecklonia cava-derived antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse mela-noma cells. Steady-state intracellular ROS levels were higher in malignant B16F10 cells than in parental, nonmetastatic B16F0 cells. Elevation of ROS by H2O2 treatment increased migration and invasion ability of B16F0 cells to level similar to that of B16F10 cells, suggesting that intracellular ROS signaling mediates the prometastatic properties of B16 mouse melanoma cells. ROS levels and the cell migration and invasion ability of B16 melanoma cells correlated with Rac1 activation and WAVE2 expression. Over-expression of dominant negative Rac1 and depletion of WAVE2 by siRNA suppressed H2O2-induced cell invasion of B16F0 and B16F10 cells. Similarly, dieckol attenuates the ROS-mediated Rac1 activation and WAVE2 expression, resulting in decreased migration and invasion of B16 melanoma cells. In addition, we found that dieckol decreases association between WAVE2 and NADPH oxidase subunit p47phox. Therefore, this finding suggests that WAVE2 acts to couple intracellular Rac1/ROS signaling to the invasive migration of B16 melanoma cells, which is inhibited by dieckol.

Keywords dieckol, invasion, migration, ROS, WAVE2

Article

Research Article

Mol. Cells 2012; 33(4): 363-369

Published online April 30, 2012 https://doi.org/10.1007/s10059-012-2285-2

Copyright © The Korean Society for Molecular and Cellular Biology.

Antioxidant Dieckol Downregulates the Rac1/ROS Signaling Pathway and Inhibits Wiskott-Aldrich Syndrome Protein (WASP)-Family Verprolin-Homologous Protein 2 (WAVE2)-Mediated Invasive Migration of B16 Mouse Melanoma Cells

Sun Joo Park*, Yong Tae Kim1, and You Jin Jeon2

Department of Chemistry, Pukyong National University, Busan 608-737, Korea, 1Department of Food Science and Biotechnology, Kunsan National University, Kunsan 573-701, Korea, 2Department of Marine Life Science, Jeju National University, Jeju 690-756, Korea

Correspondence to:*Correspondence: parksj@pknu.ac.kr

Received: December 20, 2011; Revised: February 7, 2012; Accepted: February 17, 2012

Abstract

Reactive oxygen species (ROS) generation is linked to dynamic actin cytoskeleton reorganization, which is in-volved in tumor cell motility and metastasis. Thus, inhibi-tion of ROS generation and actin polymerization in tumor cells may represent an effective anticancer strategy. However, the molecular basis of this signaling pathway is currently unknown. Here, we show that the Ecklonia cava-derived antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse mela-noma cells. Steady-state intracellular ROS levels were higher in malignant B16F10 cells than in parental, nonmetastatic B16F0 cells. Elevation of ROS by H2O2 treatment increased migration and invasion ability of B16F0 cells to level similar to that of B16F10 cells, suggesting that intracellular ROS signaling mediates the prometastatic properties of B16 mouse melanoma cells. ROS levels and the cell migration and invasion ability of B16 melanoma cells correlated with Rac1 activation and WAVE2 expression. Over-expression of dominant negative Rac1 and depletion of WAVE2 by siRNA suppressed H2O2-induced cell invasion of B16F0 and B16F10 cells. Similarly, dieckol attenuates the ROS-mediated Rac1 activation and WAVE2 expression, resulting in decreased migration and invasion of B16 melanoma cells. In addition, we found that dieckol decreases association between WAVE2 and NADPH oxidase subunit p47phox. Therefore, this finding suggests that WAVE2 acts to couple intracellular Rac1/ROS signaling to the invasive migration of B16 melanoma cells, which is inhibited by dieckol.

Keywords: dieckol, invasion, migration, ROS, WAVE2

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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