Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells

Hypoxia causes the malignant progression of tumor cells; hence, it has been considered a central issue that must be addressed for effective cancer therapy. The initiation of tumor metastasis requires invasive cell migration. Here, we show that an antioxidant peptide derived from Spirulina maxima sup...

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Main Authors: Won Suk Kim, Won Kyo Jung, Sun Joo Park
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Chemistry
Online Access:http://dx.doi.org/10.1155/2015/308602
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author Won Suk Kim
Won Kyo Jung
Sun Joo Park
author_facet Won Suk Kim
Won Kyo Jung
Sun Joo Park
author_sort Won Suk Kim
collection DOAJ
description Hypoxia causes the malignant progression of tumor cells; hence, it has been considered a central issue that must be addressed for effective cancer therapy. The initiation of tumor metastasis requires invasive cell migration. Here, we show that an antioxidant peptide derived from Spirulina maxima suppresses hypoxia-induced invasive migration of HT1080 human fibrosarcoma cells. HT1080 cells treated with a hypoxia-inducing agent, CoCl2, exhibited an increase in invasive migration and intracellular reactive oxygen species (ROS), which is associated with an increase in the expression of hypoxia-induced factor 1α (HIF1α) accompanied by the activation of PI3K/Akt and ERK1/2. The inhibition of PI3K/Akt and ERK1/2 with specific inhibitors diminished the CoCl2-induced increase in HIF1α expression and invasive cell migration. Moreover, CoCl2-induced HIF1α expression was associated with an increase in the expression of molecules downstream of β-integrin, such as N-cadherin, vimentin, and β-catenin. Therefore, the S. maxima peptide effectively attenuated the CoCl2-induced ROS generation and downregulated the HIF1α signaling pathway involving PI3K/Akt, ERK1/2, and β-integrin in cells. These results suggest that the S. maxima antioxidant peptide downregulates the HIF1α signaling pathway necessary for hypoxia-induced invasive migration of HT1080 cells by attenuating intracellular ROS. S. maxima peptide may be an effective constituent in antitumor progression products.
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spelling doaj-art-a527f721b55d48eab83e1f9af04d61b52025-02-03T01:11:30ZengWileyJournal of Chemistry2090-90632090-90712015-01-01201510.1155/2015/308602308602Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma CellsWon Suk Kim0Won Kyo Jung1Sun Joo Park2Department of Pharmaceutical Engineering, Silla University, Busan 9491, Republic of KoreaDepartment of Biomedical Engineering, Pukyong National University, Busan 8160, Republic of KoreaDepartment of Chemistry, Pukyong National University, Busan 8160, Republic of KoreaHypoxia causes the malignant progression of tumor cells; hence, it has been considered a central issue that must be addressed for effective cancer therapy. The initiation of tumor metastasis requires invasive cell migration. Here, we show that an antioxidant peptide derived from Spirulina maxima suppresses hypoxia-induced invasive migration of HT1080 human fibrosarcoma cells. HT1080 cells treated with a hypoxia-inducing agent, CoCl2, exhibited an increase in invasive migration and intracellular reactive oxygen species (ROS), which is associated with an increase in the expression of hypoxia-induced factor 1α (HIF1α) accompanied by the activation of PI3K/Akt and ERK1/2. The inhibition of PI3K/Akt and ERK1/2 with specific inhibitors diminished the CoCl2-induced increase in HIF1α expression and invasive cell migration. Moreover, CoCl2-induced HIF1α expression was associated with an increase in the expression of molecules downstream of β-integrin, such as N-cadherin, vimentin, and β-catenin. Therefore, the S. maxima peptide effectively attenuated the CoCl2-induced ROS generation and downregulated the HIF1α signaling pathway involving PI3K/Akt, ERK1/2, and β-integrin in cells. These results suggest that the S. maxima antioxidant peptide downregulates the HIF1α signaling pathway necessary for hypoxia-induced invasive migration of HT1080 cells by attenuating intracellular ROS. S. maxima peptide may be an effective constituent in antitumor progression products.http://dx.doi.org/10.1155/2015/308602
spellingShingle Won Suk Kim
Won Kyo Jung
Sun Joo Park
Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
Journal of Chemistry
title Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
title_full Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
title_fullStr Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
title_full_unstemmed Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
title_short Antioxidant Peptide Derived from Spirulina maxima Suppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells
title_sort antioxidant peptide derived from spirulina maxima suppresses hif1α induced invasive migration of ht1080 fibrosarcoma cells
url http://dx.doi.org/10.1155/2015/308602
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AT wonkyojung antioxidantpeptidederivedfromspirulinamaximasuppresseshif1ainducedinvasivemigrationofht1080fibrosarcomacells
AT sunjoopark antioxidantpeptidederivedfromspirulinamaximasuppresseshif1ainducedinvasivemigrationofht1080fibrosarcomacells