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A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways

Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this st...

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Autores principales: Yue, Shi-Jun, Zhang, Peng-Xuan, Zhu, Yue, Li, Nian-Guang, Chen, Yan-Yan, Li, Jia-Jia, Zhang, Sai, Jin, Ru-Yi, Yan, Hao, Shi, Xu-Qin, Tang, Yu-Ping, Duan, Jin-Ao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600170/
https://www.ncbi.nlm.nih.gov/pubmed/31181779
http://dx.doi.org/10.3390/molecules24112165
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author Yue, Shi-Jun
Zhang, Peng-Xuan
Zhu, Yue
Li, Nian-Guang
Chen, Yan-Yan
Li, Jia-Jia
Zhang, Sai
Jin, Ru-Yi
Yan, Hao
Shi, Xu-Qin
Tang, Yu-Ping
Duan, Jin-Ao
author_facet Yue, Shi-Jun
Zhang, Peng-Xuan
Zhu, Yue
Li, Nian-Guang
Chen, Yan-Yan
Li, Jia-Jia
Zhang, Sai
Jin, Ru-Yi
Yan, Hao
Shi, Xu-Qin
Tang, Yu-Ping
Duan, Jin-Ao
author_sort Yue, Shi-Jun
collection PubMed
description Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, wherein it revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells induced cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and regulated the extracellular signal-regulated kinase (ERK)/p38, c-Jun N-terminal kinase (JNK), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase (MEK)/ERK signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by positively regulating JNK signaling pathway and negativly regulating ERK/p38, AKT/mTOR, and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about FA derivatives.
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spelling pubmed-66001702019-07-16 A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways Yue, Shi-Jun Zhang, Peng-Xuan Zhu, Yue Li, Nian-Guang Chen, Yan-Yan Li, Jia-Jia Zhang, Sai Jin, Ru-Yi Yan, Hao Shi, Xu-Qin Tang, Yu-Ping Duan, Jin-Ao Molecules Article Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, wherein it revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells induced cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and regulated the extracellular signal-regulated kinase (ERK)/p38, c-Jun N-terminal kinase (JNK), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase (MEK)/ERK signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by positively regulating JNK signaling pathway and negativly regulating ERK/p38, AKT/mTOR, and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about FA derivatives. MDPI 2019-06-08 /pmc/articles/PMC6600170/ /pubmed/31181779 http://dx.doi.org/10.3390/molecules24112165 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yue, Shi-Jun
Zhang, Peng-Xuan
Zhu, Yue
Li, Nian-Guang
Chen, Yan-Yan
Li, Jia-Jia
Zhang, Sai
Jin, Ru-Yi
Yan, Hao
Shi, Xu-Qin
Tang, Yu-Ping
Duan, Jin-Ao
A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title_full A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title_fullStr A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title_full_unstemmed A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title_short A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways
title_sort ferulic acid derivative fxs-3 inhibits proliferation and metastasis of human lung cancer a549 cells via positive jnk signaling pathway and negative erk/p38, akt/mtor and mek/erk signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600170/
https://www.ncbi.nlm.nih.gov/pubmed/31181779
http://dx.doi.org/10.3390/molecules24112165
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