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Mol. Cells 2012; 33(2): 141-149

Published online February 29, 2012

https://doi.org/10.1007/s10059-012-2192-6

© The Korean Society for Molecular and Cellular Biology

Dieckol from Ecklonia cava Suppresses the Migration and Invasion of HT1080 Cells by Inhibiting the Focal Adhesion Kinase Pathway Downstream of Rac1-ROS Signaling

Sun Joo Park*, and You Jin Jeon1

Department of Chemistry, Pukyong National University, Busan 608-737, Korea, 1Department of Marine Life Science, Jeju National University, Jeju 690-756, Korea

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

Received: September 9, 2011; Revised: November 10, 2011; Accepted: November 30, 2011

Abstract

We have previously isolated dieckol, a nutrient polyphe-nol compound, from the brown alga, Ecklonia cava (Lee et al., 2010a). Dieckol shows both antitumor and antioxidant activity and thus is of special interest for the development of chemopreventive and chemotherapeutic agents against cancer. However, the mechanism by which dieckol exerts its antitumor activity is poorly understood. Here, we show that dieckol, derived from E. cava, inhibits migration and invasion of HT1080 cells by scavenging intracellular reactive oxygen species (ROS). H2O2 or integrin signal-media-ted ROS generation increases migration and invasion of HT1080 cells, which correlates with Rac1 activation and increased expression and phosphorylation of focal adhesion kinase (FAK). Rac1 activation is required for ROS generation. Depletion of FAK by siRNA suppresses Rac1-ROS-induced cell migration and invasion. Dieckol treatment attenuated intracellular ROS levels and activation of Rac1 as well as expression and phosphorylation of FAK. Dieckol treatment also decreases complex formation of FAK-Src-p130Cas and expression of MMP2, 9, and 13. These results suggest that the Rac1-ROS-linked cascade enhances migration and invasion of HT1080 cells by in-ducing expression of MMPs through activation of the FAK signaling pathway, whereas dieckol downregulates FAK signaling through scavenging intracellular ROS. This finding provides new insights into the mechanisms by which dieckol is able to suppress human cancer progresssion and metastasis. Therefore, we suggest that dieckol is a potential therapeutic agent for cancer treatment.

Keywords dieckol, FAK, invasion, migration, ROS

Article

Research Article

Mol. Cells 2012; 33(2): 141-149

Published online February 29, 2012 https://doi.org/10.1007/s10059-012-2192-6

Copyright © The Korean Society for Molecular and Cellular Biology.

Dieckol from Ecklonia cava Suppresses the Migration and Invasion of HT1080 Cells by Inhibiting the Focal Adhesion Kinase Pathway Downstream of Rac1-ROS Signaling

Sun Joo Park*, and You Jin Jeon1

Department of Chemistry, Pukyong National University, Busan 608-737, Korea, 1Department of Marine Life Science, Jeju National University, Jeju 690-756, Korea

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

Received: September 9, 2011; Revised: November 10, 2011; Accepted: November 30, 2011

Abstract

We have previously isolated dieckol, a nutrient polyphe-nol compound, from the brown alga, Ecklonia cava (Lee et al., 2010a). Dieckol shows both antitumor and antioxidant activity and thus is of special interest for the development of chemopreventive and chemotherapeutic agents against cancer. However, the mechanism by which dieckol exerts its antitumor activity is poorly understood. Here, we show that dieckol, derived from E. cava, inhibits migration and invasion of HT1080 cells by scavenging intracellular reactive oxygen species (ROS). H2O2 or integrin signal-media-ted ROS generation increases migration and invasion of HT1080 cells, which correlates with Rac1 activation and increased expression and phosphorylation of focal adhesion kinase (FAK). Rac1 activation is required for ROS generation. Depletion of FAK by siRNA suppresses Rac1-ROS-induced cell migration and invasion. Dieckol treatment attenuated intracellular ROS levels and activation of Rac1 as well as expression and phosphorylation of FAK. Dieckol treatment also decreases complex formation of FAK-Src-p130Cas and expression of MMP2, 9, and 13. These results suggest that the Rac1-ROS-linked cascade enhances migration and invasion of HT1080 cells by in-ducing expression of MMPs through activation of the FAK signaling pathway, whereas dieckol downregulates FAK signaling through scavenging intracellular ROS. This finding provides new insights into the mechanisms by which dieckol is able to suppress human cancer progresssion and metastasis. Therefore, we suggest that dieckol is a potential therapeutic agent for cancer treatment.

Keywords: dieckol, FAK, invasion, migration, ROS

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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