Eupalinolide A induces autophagy via the ROS/ERK signaling pathway in hepatocellular carcinoma cells <em>in vitro</em> and <em>in vivo</em>

Zhang,Yonghui; Dong,Feng; Cao,Zhihao; Wang,Tingting; Pan,Lian; Luo,Wujing; Ding,Wenxuan; Li,Jiaxin; Jin,Lishan; Liu,Huan; Zhang,Haoyang; Mu,Jinage; Han,Meiyue; Wei,Yong; Deng,Xuesong; Liu,Dan; Hao,Po; Zeng,Gang; Pang,Yi; Liu,Guiyuan; Zhen,Changlin

doi:10.3892/ijo.2022.5421

Eupalinolide A induces autophagy via the ROS/ERK signaling pathway in hepatocellular carcinoma cells in vitro and in vivo

Authors:
- Yonghui Zhang
- Feng Dong
- Zhihao Cao
- Tingting Wang
- Lian Pan
- Wujing Luo
- Wenxuan Ding
- Jiaxin Li
- Lishan Jin
- Huan Liu
- Haoyang Zhang
- Jinage Mu
- Meiyue Han
- Yong Wei
- Xuesong Deng
- Dan Liu
- Po Hao
- Gang Zeng
- Yi Pang
- Guiyuan Liu
- Changlin Zhen
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Affiliations: Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing Three Gorges Medical College, Chongqing 404120, P.R. China, Key Laboratory of Intelligent Information Processing and Control, College of Electronic and Information Engineering, Chongqing Three Gorges University, Chongqing 404110, P.R. China
Published online on: September 15, 2022 https://doi.org/10.3892/ijo.2022.5421
Article Number: 131
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma is the most common primary malignancy of the liver. The current systemic drugs used to treat hepatocellular carcinoma result in low overall survival time. It has therefore been suggested that new small‑molecule drugs should be developed for treating hepatocellular carcinoma. Eupatorium lindleyanum DC. (EL) has been used to treat numerous diseases, particularly respiratory diseases; however, to the best of our knowledge, studies have not yet fully elucidated the effect of EL on hepatocellular carcinoma. In the present study, the effect of eupalinolide A (EA), one of the extracts of EL, was evaluated on tumor growth in a xenograft model of human hepatocellular carcinoma cells, and on the proliferation and migration of hepatocellular carcinoma cell lines. Cell cycle progression and the type of cell death were then evaluated using the Cell Counting Kit 8 assay, flow cytometry, electron microscopy and western blotting. EA significantly inhibited cell proliferation and migration by arresting the cell cycle at the G₁ phase and inducing autophagy in hepatocellular carcinoma cells. EA‑induced autophagy was mediated by reactive oxygen species (ROS) and ERK signaling activation. Specific inhibitors of ROS, autophagy and ERK inhibited EA‑induced cell death and migration. In conclusion, the present study revealed that EA may inhibit the proliferation and migration of hepatocellular carcinoma cells, highlighting its potential as a promising antitumor compound for treating hepatocellular carcinoma.

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