Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and there is currently a lack of effective treatment options to control the metastasis. This study was performed to examine the mechanisms of the migration and invasion characteristics of HCC, with the aim of reducing metasta...

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Main Authors: Tsung-Chang Tsai, Wen-Tung Wu, Jen-Jie Lin, Jui-Hsin Su, Yu-Jen Wu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2022/4416611
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author Tsung-Chang Tsai
Wen-Tung Wu
Jen-Jie Lin
Jui-Hsin Su
Yu-Jen Wu
author_facet Tsung-Chang Tsai
Wen-Tung Wu
Jen-Jie Lin
Jui-Hsin Su
Yu-Jen Wu
author_sort Tsung-Chang Tsai
collection DOAJ
description Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and there is currently a lack of effective treatment options to control the metastasis. This study was performed to examine the mechanisms of the migration and invasion characteristics of HCC, with the aim of reducing metastasis by inhibiting cancer cell migration and invasion. In this study, we used Stellettin B, an active compound isolated from Stelletta sponges, as the experimental drug and evaluated its inhibition effects on cell migration and invasion in human hepatoma cells (HA22T and HepG2). MTT assay, gelatin zymography, and western blotting were employed. The results showed that Stellettin B significantly inhibited the protein expressions of MMP-2, MMP-9, and uPA, while upregulating the protein expressions of TIMP-1 and TIMP-2. The expressions of p-FAK, p-PI3K, p-AKT, p-mTOR, and MAPKs (p-JNK, p-JUN, p-MAPKp38, and p-ERK) were decreased with increasing concentrations of Stellettin B. Our results suggest that Stellettin B-dependent downregulation of MMP-2 and MMP-9 activities could be mediated by FAK/PI3K/AKT/mTOR and MAPKs signaling pathways in HA22T and HepG2 cells, preventing HCC invasion and migration.
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issn 1687-8884
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publishDate 2022-01-01
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series International Journal of Cell Biology
spelling doaj-art-11a4e22ed6b64dba9b5e5a3f6afb13292025-02-03T01:00:44ZengWileyInternational Journal of Cell Biology1687-88842022-01-01202210.1155/2022/4416611Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling PathwaysTsung-Chang Tsai0Wen-Tung Wu1Jen-Jie Lin2Jui-Hsin Su3Yu-Jen Wu4Department of NephrologyDepartment of Food Science and NutritionDepartment of Food Science and NutritionNational Museum of Marine Biology & AquariumDepartment of Food Science and NutritionHepatocellular carcinoma (HCC) is one of the most common malignant tumors, and there is currently a lack of effective treatment options to control the metastasis. This study was performed to examine the mechanisms of the migration and invasion characteristics of HCC, with the aim of reducing metastasis by inhibiting cancer cell migration and invasion. In this study, we used Stellettin B, an active compound isolated from Stelletta sponges, as the experimental drug and evaluated its inhibition effects on cell migration and invasion in human hepatoma cells (HA22T and HepG2). MTT assay, gelatin zymography, and western blotting were employed. The results showed that Stellettin B significantly inhibited the protein expressions of MMP-2, MMP-9, and uPA, while upregulating the protein expressions of TIMP-1 and TIMP-2. The expressions of p-FAK, p-PI3K, p-AKT, p-mTOR, and MAPKs (p-JNK, p-JUN, p-MAPKp38, and p-ERK) were decreased with increasing concentrations of Stellettin B. Our results suggest that Stellettin B-dependent downregulation of MMP-2 and MMP-9 activities could be mediated by FAK/PI3K/AKT/mTOR and MAPKs signaling pathways in HA22T and HepG2 cells, preventing HCC invasion and migration.http://dx.doi.org/10.1155/2022/4416611
spellingShingle Tsung-Chang Tsai
Wen-Tung Wu
Jen-Jie Lin
Jui-Hsin Su
Yu-Jen Wu
Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
International Journal of Cell Biology
title Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
title_full Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
title_fullStr Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
title_full_unstemmed Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
title_short Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways
title_sort stellettin b isolated from stelletta sp reduces migration and invasion of hepatocellular carcinoma cells through reducing activation of the mapks and fak pi3k akt mtor signaling pathways
url http://dx.doi.org/10.1155/2022/4416611
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