IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is a...

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Autores principales:	Leo Lap-Yan Wong, Ian Pak-Yan Lam, Tracy Yuk-Nar Wong, Wai-Lung Lai, Heong-Fai Liu, Lam-Lung Yeung, Yick-Pang Ching
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6383f5cc11c94fa0bf05753f7bce7372
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spelling	oai:doaj.org-article:6383f5cc11c94fa0bf05753f7bce73722021-11-18T09:03:49ZIPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.1932-620310.1371/journal.pone.0068843https://doaj.org/article/6383f5cc11c94fa0bf05753f7bce73722013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894351/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.Leo Lap-Yan WongIan Pak-Yan LamTracy Yuk-Nar WongWai-Lung LaiHeong-Fai LiuLam-Lung YeungYick-Pang ChingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68843 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leo Lap-Yan Wong Ian Pak-Yan Lam Tracy Yuk-Nar Wong Wai-Lung Lai Heong-Fai Liu Lam-Lung Yeung Yick-Pang Ching IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
description	Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.
format	article
author	Leo Lap-Yan Wong Ian Pak-Yan Lam Tracy Yuk-Nar Wong Wai-Lung Lai Heong-Fai Liu Lam-Lung Yeung Yick-Pang Ching
author_facet	Leo Lap-Yan Wong Ian Pak-Yan Lam Tracy Yuk-Nar Wong Wai-Lung Lai Heong-Fai Liu Lam-Lung Yeung Yick-Pang Ching
author_sort	Leo Lap-Yan Wong
title	IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
title_short	IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
title_full	IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
title_fullStr	IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
title_full_unstemmed	IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.
title_sort	ipa-3 inhibits the growth of liver cancer cells by suppressing pak1 and nf-κb activation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6383f5cc11c94fa0bf05753f7bce7372
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IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.

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