Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
In: Marine Drugs, Jg. 19 (2021-10-01), Heft 599
Online
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Zugriff:
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.
Titel: |
Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells
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Autor/in / Beteiligte Person: | Li, Xia ; Zhu, Yaoyao ; Jiang, Shiqing ; Zhao, Xingming ; Xie, Xiaoyu ; Ma, Jia-Hui ; Zhang, Hao ; Han, Ningning ; Ruan, Hang ; Zhang, E ; Li, Jianjiang ; Xie, Wei-Dong |
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Zeitschrift: | Marine Drugs, Jg. 19 (2021-10-01), Heft 599 |
Veröffentlichung: | MDPI AG, 2021 |
Medientyp: | unknown |
ISSN: | 1660-3397 (print) |
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