Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway

Jayasooriya,Rajapaksha  Gendara Prasad Tharanga; Lee,Yong-Gab; Kang,Chang-Hee; Lee,Kyoung-Tae; Choi,Yung  Hyun; Park,Sung-Yong; Hwang,Jae-Kwan; Kim,Gi-Young

doi:10.3892/ol.2012.968

Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway

Authors:
- Rajapaksha Gendara Prasad Tharanga Jayasooriya
- Yong-Gab Lee
- Chang-Hee Kang
- Kyoung-Tae Lee
- Yung Hyun Choi
- Sung-Yong Park
- Jae-Kwan Hwang
- Gi-Young Kim
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Affiliations: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea, Department of Biomaterials Science and Technology, Yonsei University, Seoul 120-749, Republic of Korea , Laboratory of Natural Product Chemistry, Division of Wood Chemistry and Microbiology, Department of Forest Products, Korea Forest Research Institute, Seoul 130-712, Republic of Korea, Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-051, Republic of Korea, OTTOGI Research Institute, OTTOGI Ltd., Gyeonggi-do 431-070, Republic of Korea, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea
Published online on: October 12, 2012 https://doi.org/10.3892/ol.2012.968
Pages: 341-347

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Abstract

Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.

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