New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy....
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Yuanyuan Fu [verfasserIn] Qianqian Gu [verfasserIn] Li Luo [verfasserIn] Jiecheng Xu [verfasserIn] Yuping Luo [verfasserIn] Fan Xia [verfasserIn] Fanghai Han [verfasserIn] Liang Hong [verfasserIn] Xiao-Ming Yin [verfasserIn] Zhiying Huang [verfasserIn] Min Li [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	ATG4B autophagy colorectal cancer dual-function inhibitor lysosome inhibition new anti-cancer strategy

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 12(2020), 6, p 1523
Übergeordnetes Werk:	volume:12 ; year:2020 ; number:6, p 1523

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers12061523

Katalog-ID:	DOAJ051658984

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allfieldsSound	10.3390/cancers12061523 doi (DE-627)DOAJ051658984 (DE-599)DOAJbd976d6235994b3a98f1b785d4d2baeb DE-627 ger DE-627 rakwb eng RC254-282 Yuanyuan Fu verfasserin aut New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy. ATG4B autophagy colorectal cancer dual-function inhibitor lysosome inhibition new anti-cancer strategy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Qianqian Gu verfasserin aut Li Luo verfasserin aut Jiecheng Xu verfasserin aut Yuping Luo verfasserin aut Fan Xia verfasserin aut Fanghai Han verfasserin aut Liang Hong verfasserin aut Xiao-Ming Yin verfasserin aut Zhiying Huang verfasserin aut Min Li verfasserin aut In Cancers MDPI AG, 2010 12(2020), 6, p 1523 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:6, p 1523 https://doi.org/10.3390/cancers12061523 kostenfrei https://doaj.org/article/bd976d6235994b3a98f1b785d4d2baeb kostenfrei https://www.mdpi.com/2072-6694/12/6/1523 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 6, p 1523
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authorswithroles_txt_mv	Yuanyuan Fu @@aut@@ Qianqian Gu @@aut@@ Li Luo @@aut@@ Jiecheng Xu @@aut@@ Yuping Luo @@aut@@ Fan Xia @@aut@@ Fanghai Han @@aut@@ Liang Hong @@aut@@ Xiao-Ming Yin @@aut@@ Zhiying Huang @@aut@@ Min Li @@aut@@
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callnumber-first	R - Medicine
author	Yuanyuan Fu
spellingShingle	Yuanyuan Fu misc RC254-282 misc ATG4B misc autophagy misc colorectal cancer misc dual-function inhibitor misc lysosome inhibition misc new anti-cancer strategy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function
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topic_title	RC254-282 New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function ATG4B autophagy colorectal cancer dual-function inhibitor lysosome inhibition new anti-cancer strategy
topic	misc RC254-282 misc ATG4B misc autophagy misc colorectal cancer misc dual-function inhibitor misc lysosome inhibition misc new anti-cancer strategy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc ATG4B misc autophagy misc colorectal cancer misc dual-function inhibitor misc lysosome inhibition misc new anti-cancer strategy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc ATG4B misc autophagy misc colorectal cancer misc dual-function inhibitor misc lysosome inhibition misc new anti-cancer strategy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function
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title_full	New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function
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title_sort	new anti-cancer strategy to suppress colorectal cancer growth through inhibition of atg4b and lysosome function
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title_auth	New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function
abstract	Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.
abstractGer	Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.
abstract_unstemmed	Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.
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title_short	New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function
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up_date	2024-07-03T21:35:13.174Z
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New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

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