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

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.

Influences of Microwave-Assisted Extraction Parameters on Antioxidant Activity of the Extract from Akebia trifoliata Peels

“…These compounds might partly contribute to the antioxidant activity of Akebia trifoliate peel extract. Chlorogenic acid was one of the most abundant polyphenols in many natural products and exhibited antioxidant, anti-inflammatory as well as anticancer effects (such as anti-metastatic effects and anti-proliferative activity) [ 26 , 27 , 28 , 29 ]. Besides, clinical studies indicated that chlorogenic acid could decrease the risk of metabolic syndromes and chronic diseases (cardiovascular diseases, neurodegenerative diseases and liver diseases).…”

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

“…Attenuating mitochondrial membrane potential and reciprocally modulating Bcl-2 and Bax, CGA promotes programmed cell death in A498 human kidney cancer cells, for instance [21]. Moreover, the involvement of the Bax/Bcl-2 pathway has latterly been documented in CGA-mediated apoptosis induction in lung, breast, and hepatoma cancer cells [36,56,57]. Intriguingly, in the only existing study in which CGA potentiates Doxo-mediated cytotoxic effects, Elrazik and colleagues documented a simultaneous engagement of both intrinsic and extrinsic related pathways [26].…”

“…Moreover, even though an initial CGA Phase I clinical trial has recently been concluded, demonstrating that its injection is safe and well-tolerated in recurrent high grade glioma patients, collecting safety data in a larger statistical sample is absolutely necessary to define the tolerance and pharmacokinetics of this compound (NCT02245204). Limited studies have been conducted even in preclinical models, and thus additional insights must be provided aimed at defining the CGA impact on both cancer and healthy tissues [37,57]. In this respect, we previously addressed the colony-forming ability in both OS and non-tumor mouse embryonic fibroblasts NIH 3T3 [23].…”

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

“…Anti-tumor ↓Anti-apoptotic gene Bcl-2/Bcl-XL ↑Pro-apoptotic gene Bax/Bcl-XS/Bad (34,35) ↑p38 mitogen-activated protein kinase (p38 MAPK) ↑c-Jun N-terminal Kinase (JNK) ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4…”