Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells

Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this st...

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Autores principales:	Jing-Yan Gao, Chih-Shiang Chang, Jin-Cherng Lien, Ting-Wei Chen, Jing-Lan Hu, Jing-Ru Weng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	tryptanthrin hepatocellular carcinoma apoptosis cell cycle arrest ROS Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/736384de732a4fba9f63e7ab6bdfab17
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spelling	oai:doaj.org-article:736384de732a4fba9f63e7ab6bdfab172021-11-25T16:48:36ZSynthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells10.3390/biomedicines91115272227-9059https://doaj.org/article/736384de732a4fba9f63e7ab6bdfab172021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1527https://doaj.org/toc/2227-9059Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.Jing-Yan GaoChih-Shiang ChangJin-Cherng LienTing-Wei ChenJing-Lan HuJing-Ru WengMDPI AGarticletryptanthrinhepatocellular carcinomaapoptosiscell cycle arrestROSBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1527, p 1527 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tryptanthrin hepatocellular carcinoma apoptosis cell cycle arrest ROS Biology (General) QH301-705.5
spellingShingle	tryptanthrin hepatocellular carcinoma apoptosis cell cycle arrest ROS Biology (General) QH301-705.5 Jing-Yan Gao Chih-Shiang Chang Jin-Cherng Lien Ting-Wei Chen Jing-Lan Hu Jing-Ru Weng Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
description	Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.
format	article
author	Jing-Yan Gao Chih-Shiang Chang Jin-Cherng Lien Ting-Wei Chen Jing-Lan Hu Jing-Ru Weng
author_facet	Jing-Yan Gao Chih-Shiang Chang Jin-Cherng Lien Ting-Wei Chen Jing-Lan Hu Jing-Ru Weng
author_sort	Jing-Yan Gao
title	Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
title_short	Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
title_full	Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
title_fullStr	Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
title_full_unstemmed	Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
title_sort	synthetic tryptanthrin derivatives induce cell cycle arrest and apoptosis via akt and mapks in human hepatocellular carcinoma cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/736384de732a4fba9f63e7ab6bdfab17
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Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells

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