Oncotarget

Research Papers:

Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling

Bing Han _, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen and Xiao-Juan Wang

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Oncotarget. 2017; 8:86227-86239. https://doi.org/10.18632/oncotarget.21043

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Abstract

Bing Han1,*, Yi-Qun Yu1,*, Qi-Lian Yang1, Chun-Ying Shen1 and Xiao-Juan Wang1

1Department of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China

*Co-first authors

Correspondence to:

Bing Han, email: [email protected]; [email protected]

Keywords: kaempferol, hepatocellular carcinoma (HCC), AMPK, autophagy, MAGE6

Received: July 27, 2017     Accepted: August 09, 2017     Published: September 16, 2017

ABSTRACT

In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation. Inhibition of AMPK, via AMPKα1 shRNA or dominant negative mutation, reversed above signaling changes. AMPK inhibition also largely inhibited Kaempferol-induced cytotoxicity in HCC cells. Autophagy inhibition, by 3-methyaldenine or Beclin-1 shRNA, also protected HCC cells from Kaempferol. Kaempferol downregulated melanoma antigen 6, the AMPK ubiquitin ligase, causing AMPKα1 stabilization and accumulation. We conclude that Kaempferol inhibits human HCC cells via activating AMPK signaling.


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