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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618951/ https://www.ncbi.nlm.nih.gov/pubmed/34822470 http://dx.doi.org/10.3390/md19110599 |
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author | Jiang, Shiqing Zhang, E Ruan, Hang Ma, Jiahui Zhao, Xingming Zhu, Yaoyao Xie, Xiaoyu Han, Ningning Li, Jianjiang Zhang, Hao Xie, Weidong Li, Xia |
author_facet | Jiang, Shiqing Zhang, E Ruan, Hang Ma, Jiahui Zhao, Xingming Zhu, Yaoyao Xie, Xiaoyu Han, Ningning Li, Jianjiang Zhang, Hao Xie, Weidong Li, Xia |
author_sort | Jiang, Shiqing |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8618951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86189512021-11-27 Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells Jiang, Shiqing Zhang, E Ruan, Hang Ma, Jiahui Zhao, Xingming Zhu, Yaoyao Xie, Xiaoyu Han, Ningning Li, Jianjiang Zhang, Hao Xie, Weidong Li, Xia Mar Drugs Article 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. MDPI 2021-10-22 /pmc/articles/PMC8618951/ /pubmed/34822470 http://dx.doi.org/10.3390/md19110599 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiang, Shiqing Zhang, E Ruan, Hang Ma, Jiahui Zhao, Xingming Zhu, Yaoyao Xie, Xiaoyu Han, Ningning Li, Jianjiang Zhang, Hao Xie, Weidong Li, Xia Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618951/ https://www.ncbi.nlm.nih.gov/pubmed/34822470 http://dx.doi.org/10.3390/md19110599 |
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