STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model

Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhib...

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Main Authors:	Byung-Hak Kim, Haeri Lee, Cheol Gyu Park, Ae Jin Jeong, Song-Hee Lee, Kum Hee Noh, Jong Bae Park, Chung-Gi Lee, Sun Ha Paek, Hyunggee Kim, Sang-Kyu Ye
Format:	Article
Language:	English
Published:	MDPI AG 2020-03-01
Series:	Cells
Subjects:	glioblastoma glioma stem cell (gsc) odz10117 stat3 targeted therapy
Online Access:	https://www.mdpi.com/2073-4409/9/3/722

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spelling	doaj-98507c931e764ae59a644a3ad0d1ac592020-11-25T02:01:59ZengMDPI AGCells2073-44092020-03-019372210.3390/cells9030722cells9030722STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft ModelByung-Hak Kim0Haeri Lee1Cheol Gyu Park2Ae Jin Jeong3Song-Hee Lee4Kum Hee Noh5Jong Bae Park6Chung-Gi Lee7Sun Ha Paek8Hyunggee Kim9Sang-Kyu Ye10Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, KoreaDepartment of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, KoreaCYTUS H&B Corporation, Cheongju 28159, KoreaDepartment of Neurosurgery, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, KoreaDepartment of Pharmacology, Seoul National University College of Medicine, Seoul 03080, KoreaConstitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.https://www.mdpi.com/2073-4409/9/3/722glioblastomaglioma stem cell (gsc)odz10117stat3targeted therapy
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Byung-Hak Kim Haeri Lee Cheol Gyu Park Ae Jin Jeong Song-Hee Lee Kum Hee Noh Jong Bae Park Chung-Gi Lee Sun Ha Paek Hyunggee Kim Sang-Kyu Ye
spellingShingle	Byung-Hak Kim Haeri Lee Cheol Gyu Park Ae Jin Jeong Song-Hee Lee Kum Hee Noh Jong Bae Park Chung-Gi Lee Sun Ha Paek Hyunggee Kim Sang-Kyu Ye STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model Cells glioblastoma glioma stem cell (gsc) odz10117 stat3 targeted therapy
author_facet	Byung-Hak Kim Haeri Lee Cheol Gyu Park Ae Jin Jeong Song-Hee Lee Kum Hee Noh Jong Bae Park Chung-Gi Lee Sun Ha Paek Hyunggee Kim Sang-Kyu Ye
author_sort	Byung-Hak Kim
title	STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
title_short	STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
title_full	STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
title_fullStr	STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
title_full_unstemmed	STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model
title_sort	stat3 inhibitor odz10117 suppresses glioblastoma malignancy and prolongs survival in a glioblastoma xenograft model
publisher	MDPI AG
series	Cells
issn	2073-4409
publishDate	2020-03-01
description	Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.
topic	glioblastoma glioma stem cell (gsc) odz10117 stat3 targeted therapy
url	https://www.mdpi.com/2073-4409/9/3/722
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STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model

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