Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC...

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Autores principales:	Shiqing Jiang, E Zhang, Hang Ruan, Jiahui Ma, Xingming Zhao, Yaoyao Zhu, Xiaoyu Xie, Ningning Han, Jianjiang Li, Hao Zhang, Weidong Xie, Xia Li
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Act V CRC PI3K/AKT apoptosis mitochondrial Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a3811ae233a94ee9961261caca143caa
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spelling	oai:doaj.org-article:a3811ae233a94ee9961261caca143caa2021-11-25T18:12:43ZActinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells10.3390/md191105991660-3397https://doaj.org/article/a3811ae233a94ee9961261caca143caa2021-10-01T00:00:00Zhttps://www.mdpi.com/1660-3397/19/11/599https://doaj.org/toc/1660-3397Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.Shiqing JiangE ZhangHang RuanJiahui MaXingming ZhaoYaoyao ZhuXiaoyu XieNingning HanJianjiang LiHao ZhangWeidong XieXia LiMDPI AGarticleAct VCRCPI3K/AKTapoptosismitochondrialBiology (General)QH301-705.5ENMarine Drugs, Vol 19, Iss 599, p 599 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Act V CRC PI3K/AKT apoptosis mitochondrial Biology (General) QH301-705.5
spellingShingle	Act V CRC PI3K/AKT apoptosis mitochondrial Biology (General) QH301-705.5 Shiqing Jiang E Zhang Hang Ruan Jiahui Ma Xingming Zhao Yaoyao Zhu Xiaoyu Xie Ningning Han Jianjiang Li Hao Zhang Weidong Xie Xia Li Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
description	Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.
format	article
author	Shiqing Jiang E Zhang Hang Ruan Jiahui Ma Xingming Zhao Yaoyao Zhu Xiaoyu Xie Ningning Han Jianjiang Li Hao Zhang Weidong Xie Xia Li
author_facet	Shiqing Jiang E Zhang Hang Ruan Jiahui Ma Xingming Zhao Yaoyao Zhu Xiaoyu Xie Ningning Han Jianjiang Li Hao Zhang Weidong Xie Xia Li
author_sort	Shiqing Jiang
title	Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
title_short	Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
title_full	Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
title_fullStr	Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
title_full_unstemmed	Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
title_sort	actinomycin v induces apoptosis associated with mitochondrial and pi3k/akt pathways in human crc cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a3811ae233a94ee9961261caca143caa
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Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

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