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Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the most common primary malignant tumors of the digestive system. Compound 5-chloro-N′-(2,4-dimethoxybenzylidene)-1H-indole-2-carbohydrazide (IHZ-1/ZJQ-24) is a novel indole hydrazide derivative. In a recent study, we demonstrated that IHZ-1 inhibits tumor growth a...

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Autores principales: Sun, Manting, Liu, Dan, Yuan, Yang, Dan, Juhua, Jia, Shuting, Luo, Ying, Liu, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858831/
https://www.ncbi.nlm.nih.gov/pubmed/35198445
http://dx.doi.org/10.3389/fonc.2022.811747
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author Sun, Manting
Liu, Dan
Yuan, Yang
Dan, Juhua
Jia, Shuting
Luo, Ying
Liu, Jing
author_facet Sun, Manting
Liu, Dan
Yuan, Yang
Dan, Juhua
Jia, Shuting
Luo, Ying
Liu, Jing
author_sort Sun, Manting
collection PubMed
description Hepatocellular carcinoma is one of the most common primary malignant tumors of the digestive system. Compound 5-chloro-N′-(2,4-dimethoxybenzylidene)-1H-indole-2-carbohydrazide (IHZ-1/ZJQ-24) is a novel indole hydrazide derivative. In a recent study, we demonstrated that IHZ-1 inhibits tumor growth and induces cell apoptosis through inhibiting the kinase activity of mTORC1 without activation of AKT, which is associated with JNK/IRS-1 activation. However, the impact and mechanisms of JNK activation by IHZ-1 in hepatocellular carcinoma remains entirely unknown. Here, we find that IHZ-1 increases the generation of intracellular ROS and enhances autophagy. The phosphorylation of JNK induced by IHZ-1 was reversed by the decreased ROS level. Moreover, inhibition of ROS/JNK or autophagy equally attenuated apoptotic effect induced by IHZ-1. Our findings suggest that the activation of JNK by IHZ-1 treatment is dependent on the generation of ROS that mediates apoptosis and autophagy in hepatocellular carcinoma.
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spelling pubmed-88588312022-02-22 Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma Sun, Manting Liu, Dan Yuan, Yang Dan, Juhua Jia, Shuting Luo, Ying Liu, Jing Front Oncol Oncology Hepatocellular carcinoma is one of the most common primary malignant tumors of the digestive system. Compound 5-chloro-N′-(2,4-dimethoxybenzylidene)-1H-indole-2-carbohydrazide (IHZ-1/ZJQ-24) is a novel indole hydrazide derivative. In a recent study, we demonstrated that IHZ-1 inhibits tumor growth and induces cell apoptosis through inhibiting the kinase activity of mTORC1 without activation of AKT, which is associated with JNK/IRS-1 activation. However, the impact and mechanisms of JNK activation by IHZ-1 in hepatocellular carcinoma remains entirely unknown. Here, we find that IHZ-1 increases the generation of intracellular ROS and enhances autophagy. The phosphorylation of JNK induced by IHZ-1 was reversed by the decreased ROS level. Moreover, inhibition of ROS/JNK or autophagy equally attenuated apoptotic effect induced by IHZ-1. Our findings suggest that the activation of JNK by IHZ-1 treatment is dependent on the generation of ROS that mediates apoptosis and autophagy in hepatocellular carcinoma. Frontiers Media S.A. 2022-02-07 /pmc/articles/PMC8858831/ /pubmed/35198445 http://dx.doi.org/10.3389/fonc.2022.811747 Text en Copyright © 2022 Sun, Liu, Yuan, Dan, Jia, Luo and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sun, Manting
Liu, Dan
Yuan, Yang
Dan, Juhua
Jia, Shuting
Luo, Ying
Liu, Jing
Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title_full Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title_fullStr Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title_full_unstemmed Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title_short Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma
title_sort indole hydrazide compound ihz-1 induces apoptosis and autophagy via activation of ros/jnk pathway in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858831/
https://www.ncbi.nlm.nih.gov/pubmed/35198445
http://dx.doi.org/10.3389/fonc.2022.811747
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