Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aime...

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Autores principales:	Kunyan He, Guang-Xing Wang, Li-Nan Zhao, Xiao-Fang Cui, Xian-Bin Su, Yi Shi, Tian-Pei Xie, Shang-Wei Hou, Ze-Guang Han
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cinobufagin EGFR glioblastoma PTEN Chansu Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cebf564c4d7442b68cbe99b6f2dd17bc
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spelling	oai:doaj.org-article:cebf564c4d7442b68cbe99b6f2dd17bc2021-12-02T01:10:40ZCinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion1663-981210.3389/fphar.2021.775602https://doaj.org/article/cebf564c4d7442b68cbe99b6f2dd17bc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.775602/fullhttps://doaj.org/toc/1663-9812Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aimed to identify a potent compound against EGFR-driven tumor. We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects. Cinobufagin also strongly inhibited the proliferation of carcinoma cell lines with wild-type or mutant EGFR expression. In contrast, the compound only weakly inhibited the proliferation of cancer cells with low or without EGFR expression. Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells. In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors. Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.Kunyan HeGuang-Xing WangLi-Nan ZhaoXiao-Fang CuiXian-Bin SuYi ShiTian-Pei XieShang-Wei HouShang-Wei HouZe-Guang HanZe-Guang HanFrontiers Media S.A.articlecinobufaginEGFRglioblastomaPTENChansuTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cinobufagin EGFR glioblastoma PTEN Chansu Therapeutics. Pharmacology RM1-950
spellingShingle	cinobufagin EGFR glioblastoma PTEN Chansu Therapeutics. Pharmacology RM1-950 Kunyan He Guang-Xing Wang Li-Nan Zhao Xiao-Fang Cui Xian-Bin Su Yi Shi Tian-Pei Xie Shang-Wei Hou Shang-Wei Hou Ze-Guang Han Ze-Guang Han Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
description	Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aimed to identify a potent compound against EGFR-driven tumor. We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects. Cinobufagin also strongly inhibited the proliferation of carcinoma cell lines with wild-type or mutant EGFR expression. In contrast, the compound only weakly inhibited the proliferation of cancer cells with low or without EGFR expression. Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells. In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors. Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.
format	article
author	Kunyan He Guang-Xing Wang Li-Nan Zhao Xiao-Fang Cui Xian-Bin Su Yi Shi Tian-Pei Xie Shang-Wei Hou Shang-Wei Hou Ze-Guang Han Ze-Guang Han
author_facet	Kunyan He Guang-Xing Wang Li-Nan Zhao Xiao-Fang Cui Xian-Bin Su Yi Shi Tian-Pei Xie Shang-Wei Hou Shang-Wei Hou Ze-Guang Han Ze-Guang Han
author_sort	Kunyan He
title	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
title_short	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
title_full	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
title_fullStr	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
title_full_unstemmed	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion
title_sort	cinobufagin is a selective anti-cancer agent against tumors with egfr amplification and pten deletion
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cebf564c4d7442b68cbe99b6f2dd17bc
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Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion

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