α-Hederin inhibits the platelet activating factor-induced metastasis of HCC cells through disruption of PAF/PTAFR axis cascaded STAT3/MMP-2 expression.

Abstract

Metastasis remains a crucial obstacle to the clinical treatment of hepatocellular carcinoma (HCC). Investigating the potential anti-tumor compounds from medicinal herb against HCC metastasis is of particular interest. As a triterpenoid saponin, α-Hederin has been reported to exhibit cytotoxicity for diverse cancer cell lines by inducing mitochondrial related apoptosis or autophagic cell death. Nevertheless, little is known about the inhibitory effect of α-Hederin on the metastasis of HCC and its underlying mechanisms. Here, we integrated well-established target prediction webtool and molecular docking methods to predict the potential targets for α-Hederin, and finally focused on PTAFR, the receptor for platelet-activating factor (PAF). Activation of PAF/PTAFR pathways has been reported to be contribution to the initiation and progression of cancer. We showed for the first time that non-cytotoxic concentration of α-Hederin inhibited cell migration and invasion induced by PAF in HCC cells, as well as lung metastasis in vivo. Moreover, we demonstrated α-Hederin reduced the PAF-induced matrix metalloproteinase-2 expression through inhibiting the activation of STAT3 in PAF stimulated HCC cells. These findings suggest that α-Hederin functions as a prospective inhibitor of PTAFR and may be utilized as an optional candidate for treatment of HCC.

• Authors: Linna Cao, Yiwei Zhang, Jinxia Mi, Zhanhao Shi, Zhaoqin Fang, Dongwei Jia, Zhiqiang Pan, Peike Peng
• Journal: Pharmacological research (Pharmacol Res) Vol. 178 Pg. 106180 (04 2022) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 35288308 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• DNA-Binding Proteins
• PCLAF protein, human
• Platelet Activating Factor
• Platelet Membrane Glycoproteins
• Receptors, G-Protein-Coupled
• STAT3 Transcription Factor
• STAT3 protein, human
• Saponins
• platelet activating factor receptor
• Pulsatilla saponin A
• Oleanolic Acid
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• DNA-Binding Proteins (metabolism)
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Matrix Metalloproteinase 2 (metabolism)
• Molecular Docking Simulation
• Neoplasm Metastasis
• Oleanolic Acid (pharmacology)
• Platelet Activating Factor (antagonists & inhibitors, metabolism)
• Platelet Membrane Glycoproteins (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• STAT3 Transcription Factor
• Saponins (pharmacology)
• Signal Transduction (drug effects)