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AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, t...

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Autores principales: Su, Chia-Cheng, Hsieh, Kun-Lin, Liu, Po-Len, Yeh, Hsin-Chih, Huang, Shu-Pin, Fang, Shih-Hua, Cheng, Wei-Chung, Huang, Kuan-Hua, Chiu, Fang-Yen, Lin, I-Ling, Huang, Ming-Yii, Li, Chia-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480054/
https://www.ncbi.nlm.nih.gov/pubmed/30987073
http://dx.doi.org/10.3390/ijms20071647
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author Su, Chia-Cheng
Hsieh, Kun-Lin
Liu, Po-Len
Yeh, Hsin-Chih
Huang, Shu-Pin
Fang, Shih-Hua
Cheng, Wei-Chung
Huang, Kuan-Hua
Chiu, Fang-Yen
Lin, I-Ling
Huang, Ming-Yii
Li, Chia-Yang
author_facet Su, Chia-Cheng
Hsieh, Kun-Lin
Liu, Po-Len
Yeh, Hsin-Chih
Huang, Shu-Pin
Fang, Shih-Hua
Cheng, Wei-Chung
Huang, Kuan-Hua
Chiu, Fang-Yen
Lin, I-Ling
Huang, Ming-Yii
Li, Chia-Yang
author_sort Su, Chia-Cheng
collection PubMed
description Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial–mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.
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spelling pubmed-64800542019-04-29 AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway Su, Chia-Cheng Hsieh, Kun-Lin Liu, Po-Len Yeh, Hsin-Chih Huang, Shu-Pin Fang, Shih-Hua Cheng, Wei-Chung Huang, Kuan-Hua Chiu, Fang-Yen Lin, I-Ling Huang, Ming-Yii Li, Chia-Yang Int J Mol Sci Article Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial–mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer. MDPI 2019-04-03 /pmc/articles/PMC6480054/ /pubmed/30987073 http://dx.doi.org/10.3390/ijms20071647 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
Su, Chia-Cheng
Hsieh, Kun-Lin
Liu, Po-Len
Yeh, Hsin-Chih
Huang, Shu-Pin
Fang, Shih-Hua
Cheng, Wei-Chung
Huang, Kuan-Hua
Chiu, Fang-Yen
Lin, I-Ling
Huang, Ming-Yii
Li, Chia-Yang
AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title_full AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title_fullStr AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title_full_unstemmed AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title_short AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway
title_sort aicar induces apoptosis and inhibits migration and invasion in prostate cancer cells through an ampk/mtor-dependent pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480054/
https://www.ncbi.nlm.nih.gov/pubmed/30987073
http://dx.doi.org/10.3390/ijms20071647
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