Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9

Abstract Metastasis is the crucial mechanism to cause high mortality in lung cancer. Degradation of extracellular matrix (ECM) by proteolytic enzymes, especially matrix metalloproteinases (MMPs), is a key process for promoting cancer cell migration and invasion. Therefore, targeting MMPs might be a...

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Main Authors: Jih‐Tung Pai, Chia‐Yun Hsu, Yei‐San Hsieh, Tsung‐Yu Tsai, Kuo‐Tai Hua, Meng‐Shih Weng
Format: Article
Language:English
Published: Wiley 2020-03-01
Series:Food Science & Nutrition
Subjects:
Online Access:https://doi.org/10.1002/fsn3.1439
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author Jih‐Tung Pai
Chia‐Yun Hsu
Yei‐San Hsieh
Tsung‐Yu Tsai
Kuo‐Tai Hua
Meng‐Shih Weng
author_facet Jih‐Tung Pai
Chia‐Yun Hsu
Yei‐San Hsieh
Tsung‐Yu Tsai
Kuo‐Tai Hua
Meng‐Shih Weng
author_sort Jih‐Tung Pai
collection DOAJ
description Abstract Metastasis is the crucial mechanism to cause high mortality in lung cancer. Degradation of extracellular matrix (ECM) by proteolytic enzymes, especially matrix metalloproteinases (MMPs), is a key process for promoting cancer cell migration and invasion. Therefore, targeting MMPs might be a strategy for lung cancer metastasis suppression. Honokiol, a biological active component of Magnolia officinalis, has been indicated to suppress lung cancer tumorigenesis through epigenetic regulation. However, the regulation of MMPs‐mediated migration and invasion by honokiol through epigenetic regulation in lung cancer is still a mystery. In the present study, the migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment. The proteolytic activity of MMP‐9, rather than MMP‐2, was inhibited in honokiol‐treated H1299 cells. Honokiol‐inhibited MMP‐9 expression was through promoting MMP‐9 protein degradation rather than suppressing transcription mechanism. Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl‐α‐tubulin, was accumulated after honokiol incubation. The disassociation of MMP‐9 with hyper‐acetylated heat shock protein 90 (Hsp90) was observed resulting in MMP‐9 degradation after honokiol treatment. Meanwhile, honokiol‐suppressed MMP‐9 expression and invasion ability of H1299 lung cancer cells was rescued by HDAC6 overexpression. Accordingly, the results suggested that the suppression of migration and invasion activities by honokiol was through inhibiting HDAC6‐mediated Hsp90/MMP‐9 interaction and followed by MMP‐9 degradation in lung cancer.
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spelling doaj.art-bc2756dd1420472eba1a3aae08baecb22024-04-05T09:21:41ZengWileyFood Science & Nutrition2048-71772020-03-01831534154510.1002/fsn3.1439Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9Jih‐Tung Pai0Chia‐Yun Hsu1Yei‐San Hsieh2Tsung‐Yu Tsai3Kuo‐Tai Hua4Meng‐Shih Weng5Division of Hematology and Oncology Tao‐Yuan General Hospital Ministry of Health and Welfare Taoyuan City TaiwanDepartment of Nutritional Science Fu Jen Catholic University New Taipei city TaiwanDepartment of Chest Surgery Tao‐Yuan General Hospital Ministry of Health and Welfare Taoyuan City TaiwanDepartment of Food Science Fu Jen Catholic University New Taipei City TaiwanGraduate Institute of Toxicology College of Medicine National Taiwan University Taipei TaiwanDepartment of Nutritional Science Fu Jen Catholic University New Taipei city TaiwanAbstract Metastasis is the crucial mechanism to cause high mortality in lung cancer. Degradation of extracellular matrix (ECM) by proteolytic enzymes, especially matrix metalloproteinases (MMPs), is a key process for promoting cancer cell migration and invasion. Therefore, targeting MMPs might be a strategy for lung cancer metastasis suppression. Honokiol, a biological active component of Magnolia officinalis, has been indicated to suppress lung cancer tumorigenesis through epigenetic regulation. However, the regulation of MMPs‐mediated migration and invasion by honokiol through epigenetic regulation in lung cancer is still a mystery. In the present study, the migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment. The proteolytic activity of MMP‐9, rather than MMP‐2, was inhibited in honokiol‐treated H1299 cells. Honokiol‐inhibited MMP‐9 expression was through promoting MMP‐9 protein degradation rather than suppressing transcription mechanism. Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl‐α‐tubulin, was accumulated after honokiol incubation. The disassociation of MMP‐9 with hyper‐acetylated heat shock protein 90 (Hsp90) was observed resulting in MMP‐9 degradation after honokiol treatment. Meanwhile, honokiol‐suppressed MMP‐9 expression and invasion ability of H1299 lung cancer cells was rescued by HDAC6 overexpression. Accordingly, the results suggested that the suppression of migration and invasion activities by honokiol was through inhibiting HDAC6‐mediated Hsp90/MMP‐9 interaction and followed by MMP‐9 degradation in lung cancer.https://doi.org/10.1002/fsn3.1439HDAC6honokiolHsp90hyperacetylationmatrix metalloproteinases (MMPs)
spellingShingle Jih‐Tung Pai
Chia‐Yun Hsu
Yei‐San Hsieh
Tsung‐Yu Tsai
Kuo‐Tai Hua
Meng‐Shih Weng
Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
Food Science & Nutrition
HDAC6
honokiol
Hsp90
hyperacetylation
matrix metalloproteinases (MMPs)
title Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
title_full Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
title_fullStr Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
title_full_unstemmed Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
title_short Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
title_sort suppressing migration and invasion of h1299 lung cancer cells by honokiol through disrupting expression of an hdac6 mediated matrix metalloproteinase 9
topic HDAC6
honokiol
Hsp90
hyperacetylation
matrix metalloproteinases (MMPs)
url https://doi.org/10.1002/fsn3.1439
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