Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

It was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the comp...

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Main Authors:	Yu-Ching Fan, Kai-Chen Hsu, Tony-Eight Lin, Dietmar Zechner, Sung-Po Hsu, Yuan-Chin Tsai
Format:	Article
Language:	English
Published:	MDPI AG 2021-08-01
Series:	Biology
Subjects:	MLK1 androgen receptor prostate cancer pancreatic cancer
Online Access:	https://www.mdpi.com/2079-7737/10/8/742

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spelling	doaj-880459c4417a4fcfab9a135139aedd012021-08-26T13:32:09ZengMDPI AGBiology2079-77372021-08-011074274210.3390/biology10080742Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic CancersYu-Ching Fan0Kai-Chen Hsu1Tony-Eight Lin2Dietmar Zechner3Sung-Po Hsu4Yuan-Chin Tsai5PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, TaiwanPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanInstitute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059 Rostock, GermanyDepartment of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, TaiwanIt was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the compound library of the National Cancer Institute (NCI) using a MLK1 protein structure. The inhibitory effects of MLK1 were validated by an in vitro kinase assay and by monitoring phosphorylation signaling, and the anti-proliferation function was shown in several prostate and pancreatic cancer cell lines. We also demonstrated anti-tumor ability and prevention of cancer-related weight loss in a syngeneic orthotopic mouse model of pancreatic cancer that mimicked the tumor growth environment in the pancreas. Our results demonstrate that the MLK1 inhibitor is an anti-tumor agent for malignant prostate and pancreatic cancers.https://www.mdpi.com/2079-7737/10/8/742MLK1androgen receptorprostate cancerpancreatic cancer
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Yu-Ching Fan Kai-Chen Hsu Tony-Eight Lin Dietmar Zechner Sung-Po Hsu Yuan-Chin Tsai
spellingShingle	Yu-Ching Fan Kai-Chen Hsu Tony-Eight Lin Dietmar Zechner Sung-Po Hsu Yuan-Chin Tsai Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers Biology MLK1 androgen receptor prostate cancer pancreatic cancer
author_facet	Yu-Ching Fan Kai-Chen Hsu Tony-Eight Lin Dietmar Zechner Sung-Po Hsu Yuan-Chin Tsai
author_sort	Yu-Ching Fan
title	Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers
title_short	Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers
title_full	Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers
title_fullStr	Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers
title_full_unstemmed	Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers
title_sort	investigation of anti-tumor effects of an mlk1 inhibitor in prostate and pancreatic cancers
publisher	MDPI AG
series	Biology
issn	2079-7737
publishDate	2021-08-01
description	It was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the compound library of the National Cancer Institute (NCI) using a MLK1 protein structure. The inhibitory effects of MLK1 were validated by an in vitro kinase assay and by monitoring phosphorylation signaling, and the anti-proliferation function was shown in several prostate and pancreatic cancer cell lines. We also demonstrated anti-tumor ability and prevention of cancer-related weight loss in a syngeneic orthotopic mouse model of pancreatic cancer that mimicked the tumor growth environment in the pancreas. Our results demonstrate that the MLK1 inhibitor is an anti-tumor agent for malignant prostate and pancreatic cancers.
topic	MLK1 androgen receptor prostate cancer pancreatic cancer
url	https://www.mdpi.com/2079-7737/10/8/742
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Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

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