Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level

Abstract Currently, no frontline treatment is effective for the late-stage colorectal cancer (CRC). Understanding the molecular differences in different stages of CRC can help us to identify the critical therapeutic targets for designing therapeutic strategy. Our data show that c-Myc protein is high...

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Autores principales:	Xianjing Hu, Sarwat Fatima, Minting Chen, Tao Huang, Yuen Wa Chen, Ruihong Gong, Hoi Leong Xavier Wong, Rongmin Yu, Liyan Song, Hiu Yee Kwan, Zhaoxiang Bian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/48a7c6e3af874158bb18f8448c34d87e
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spelling	oai:doaj.org-article:48a7c6e3af874158bb18f8448c34d87e2021-11-07T12:05:20ZDihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level10.1038/s41419-021-04247-w2041-4889https://doaj.org/article/48a7c6e3af874158bb18f8448c34d87e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04247-whttps://doaj.org/toc/2041-4889Abstract Currently, no frontline treatment is effective for the late-stage colorectal cancer (CRC). Understanding the molecular differences in different stages of CRC can help us to identify the critical therapeutic targets for designing therapeutic strategy. Our data show that c-Myc protein is highly expressed in late-stage CRC when compared with early-stage CRC in both clinical samples and in cell lines representing different cancer stages. Given that c-Myc is a well-known oncogenic driver in CRC, its high expression in the late-stage CRC may represent a critical therapeutic target for treating the cancer. Dihydroartemisinin treatment significantly increases c-Myc protein degradation and hence reduces its expression in CRC. The treatment also reduces CRC cell viability. Interestingly, dihydroartemisinin exhibits a more potent growth-inhibitory effect in late-stage CRC than the early-stage CRC. The treatment also possesses potent growth-inhibitory effects in mouse models bearing c-Myc-overexpressed CRC. The reduced c-Myc level and its reduced transcriptional activity reduce the expressions of acetyl-CoA carboxylase, fatty acid synthase, carnitine–palmitoyltransferase-1, and medium-chain acyl-CoA dehydrogenase in the cancer cells. Lipidomics study also shows that dihydroartemisinin treatment changes the metabolic phenotypes in CRC, reduces oxygen consumption, respiration, and ATP production, hence reduces the cell proliferation and induces apoptosis. Our study provides strong pharmacological evidence to support the translation of dihydroartemisinin for the treatment of late-stage CRC by targeting c-Myc.Xianjing HuSarwat FatimaMinting ChenTao HuangYuen Wa ChenRuihong GongHoi Leong Xavier WongRongmin YuLiyan SongHiu Yee KwanZhaoxiang BianNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Xianjing Hu Sarwat Fatima Minting Chen Tao Huang Yuen Wa Chen Ruihong Gong Hoi Leong Xavier Wong Rongmin Yu Liyan Song Hiu Yee Kwan Zhaoxiang Bian Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
description	Abstract Currently, no frontline treatment is effective for the late-stage colorectal cancer (CRC). Understanding the molecular differences in different stages of CRC can help us to identify the critical therapeutic targets for designing therapeutic strategy. Our data show that c-Myc protein is highly expressed in late-stage CRC when compared with early-stage CRC in both clinical samples and in cell lines representing different cancer stages. Given that c-Myc is a well-known oncogenic driver in CRC, its high expression in the late-stage CRC may represent a critical therapeutic target for treating the cancer. Dihydroartemisinin treatment significantly increases c-Myc protein degradation and hence reduces its expression in CRC. The treatment also reduces CRC cell viability. Interestingly, dihydroartemisinin exhibits a more potent growth-inhibitory effect in late-stage CRC than the early-stage CRC. The treatment also possesses potent growth-inhibitory effects in mouse models bearing c-Myc-overexpressed CRC. The reduced c-Myc level and its reduced transcriptional activity reduce the expressions of acetyl-CoA carboxylase, fatty acid synthase, carnitine–palmitoyltransferase-1, and medium-chain acyl-CoA dehydrogenase in the cancer cells. Lipidomics study also shows that dihydroartemisinin treatment changes the metabolic phenotypes in CRC, reduces oxygen consumption, respiration, and ATP production, hence reduces the cell proliferation and induces apoptosis. Our study provides strong pharmacological evidence to support the translation of dihydroartemisinin for the treatment of late-stage CRC by targeting c-Myc.
format	article
author	Xianjing Hu Sarwat Fatima Minting Chen Tao Huang Yuen Wa Chen Ruihong Gong Hoi Leong Xavier Wong Rongmin Yu Liyan Song Hiu Yee Kwan Zhaoxiang Bian
author_facet	Xianjing Hu Sarwat Fatima Minting Chen Tao Huang Yuen Wa Chen Ruihong Gong Hoi Leong Xavier Wong Rongmin Yu Liyan Song Hiu Yee Kwan Zhaoxiang Bian
author_sort	Xianjing Hu
title	Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
title_short	Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
title_full	Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
title_fullStr	Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
title_full_unstemmed	Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level
title_sort	dihydroartemisinin is potential therapeutics for treating late-stage crc by targeting the elevated c-myc level
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/48a7c6e3af874158bb18f8448c34d87e
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Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting the elevated c-Myc level

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