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Chlorogenic acid inhibits proliferation in human hepatoma cells by suppressing noncanonical NF-κB signaling pathway and triggering mitochondrial apoptosis

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Abstract

Chlorogenic acid (CGA), a phenylpropanoid derived from Eucommia ulmoides Oliver, has been shown to exhibit potent cytotoxic and anti-proliferative activities against several human cancers. However, the effects of CGA on hepatocellular carcinoma (HCC) and the underlying mechanisms have not been intensively studied. In this study, the CGA treatment effects on the viability of human hepatoma cells were investigated by MTT assay. Our data showed that CGA could dose-dependently inhibit the activity of human hepatoma cells Hep-G2 and Huh-7, but did not affect the activity and growth of normal human hepatocyte QSG-7701. The genes and pathways influenced by CGA treatment were explored by RNA sequencing and bioinformatics analysis, which identified 323 differentially expressed genes (DEGs) involved in multiple pharmacological signaling pathways such as MAPK, NF-κB, apoptosis and TGF-β signaling pathways. Further analyses by real-time quantitative PCR, Western blot and flow cytometry revealed that CGA effectually suppressed the noncanonical NF-κB signaling pathway, meanwhile it activated the mitochondrial apoptosis of HCC by upregulation of the BH3-only protein Bcl-2 binding component 3 (BBC3). Our findings demonstrated the potential of CGA in suppressing human hepatoma cells and provided a new insight into the anti-cancer mechanism of CGA.

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Acknowledgements

We thank the Teaching and Research Core Facility at College of Life Sciences, NWAFU, for their support in this work.

Funding

This work is supported by 13th Five Year National Key Research and Development Program of China (2017YFD0600702).

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Authors and Affiliations

  1. College of Life Sciences, Northwest A & F University, Yangling, 712100, Shaanxi, China

    Yanfei Jiang, Hao Nan, Na Shi, Wenfang Hao, Juane Dong & Hongying Chen

  2. College of Chemistry & Pharmacy, Northwest A & F University, Yangling, 712100, Shaanxi, China

    Yanfei Jiang

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Contributions

HC and JD conceived and designed this research. YJ, HN and NS performed the experiments. YJ, HC and WH analyzed the data. HC, YJ and JD wrote the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Juane Dong or Hongying Chen.

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Jiang, Y., Nan, H., Shi, N. et al. Chlorogenic acid inhibits proliferation in human hepatoma cells by suppressing noncanonical NF-κB signaling pathway and triggering mitochondrial apoptosis. Mol Biol Rep 48, 2351–2364 (2021). https://doi.org/10.1007/s11033-021-06267-3

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