ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2015
Ammonium chloride inhibits autophagy of hepatocellular carcinoma cells through SMAD2 signaling.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
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- Identification and analysis of circRNA-miRNA-mRNA regulatory network in hepatocellular carcinoma.IET systems biology · 2020Article
- A study of autophagy in hemocytes of the Pacific oyster,Autophagy · 2019Article
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- The metabolic waste ammonium regulates mTORC2 and mTORC1 signaling.Scientific reports · 2017Article
- Norcantharidin induces autophagy-related prostate cancer cell death through Beclin-1 upregulation by miR-129-5p suppression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4.Oncotarget · 2016Article
- RETRACTED: The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late StagesInternational journal of molecular sciences · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a cellular degradation process for the clearance of damaged or superfluous proteins and organelles, the recycling of which serves as an alternative energy source during periods of metabolic stress to maintain cell homeostasis and viability. The anti-necrotic function of autophagy is critical for tumorigenesis of many tumor cells, including hepatocellular carcinoma (HCC). However, the underlying mechanism is not clarified yet. Ammonium chloride (NH4Cl) is a well-known autophagy inhibitor, whereas its interaction with SMAD2 signaling pathway has not been reported previously. Here, we show that NH4Cl significantly inhibited rapamycin-induced autophagy in HCC cells through decreasing the levels of Beclin-1, autophagy-related protein 7 (ATG7), p62, and autophagosome marker LC3 and significantly decreased the level of phosphorylated SMAD2 in rapamycin-treated HCC cells. In order to find out whether NH4Cl may inhibit the autophagy in rapamycin-treated HCC cells through inhibition of SMAD2 signaling, we used transforming growth factor β1 (TGFβ1) to induce phosphorylation of SMAD2 in HCC cells. We found that induction of SMAD2 in HCC cells completely abolished the inhibitory effect of NH4Cl on rapamycin-induced autophagy in HCC cells, suggesting that NH4Cl inhibits autophagy of HCC cells through inhibiting SMAD2 signaling.
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