Oncotarget

Research Papers:

Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum stress-CHOP-autophagy signaling pathway

Haiqing Guo, Wei Lin, Xiangying Zhang, Xiaohui Zhang, Zhongjie Hu, Liying Li, Zhongping Duan, Jing Zhang and Feng Ren _

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Oncotarget. 2017; 8:82207-82216. https://doi.org/10.18632/oncotarget.19200

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Abstract

Haiqing Guo1,*, Wei Lin1,*, Xiangying Zhang2, Xiaohui Zhang1, Zhongjie Hu1, Liying Li3, Zhongping Duan4, Jing Zhang1 and Feng Ren2

1Department of Hepatitis C and Drug‑Induced Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China

2Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, China

3Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China

4Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China

*These authors have contributed equally to this work

Correspondence to:

Feng Ren, email: [email protected]

Jing Zhang, email: [email protected]

Keywords: kaempferol, hepatocellular carcinoma cell, endoplasmic reticulum stress, C/EBP homologous protein, autophagy

Received: October 24, 2016     Accepted: June 11, 2017     Published: July 12, 2017

ABSTRACT

Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis. We further hypothesized that kaempferol can induce autophagy via endoplasmic reticulum (ER) stress pathway. Indeed, blocking ER stress by 4-phenyl butyric acid (4-PBA) or knockdown of CCAAT/enhancer-binding protein homologous protein (CHOP) with siRNA alleviated kaempferol-induced HepG2 or Huh7 cells autophagy; while transfection with plasmid overexpressing CHOP reversed the effect of 4-PBA on kaempferol-induced autophagy. Our results demonstrated that kaempferol induced hepatocarcinoma cell death via ER stress and CHOP-autophagy signaling pathway; kaempferol may be used as a potential chemopreventive agent for patients with hepatocellular carcinoma.


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