Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase.

Abstract

Glycycoumarin (GCM) is a major bioactive coumarin compound isolated from licorice and the anti-cancer activity of GCM has not been scientifically addressed. In the present study, we have tested the anti-liver cancer activity of GCM using both in vitro and in vivo models and found for the first time that GCM possesses a potent activity against liver cancer evidenced by cell growth inhibition and apoptosis induction in vitro and tumor reduction in vivo. Mechanistically, GCM was able to bind to and inactivate oncogenic kinase T-LAK cell-originated protein kinase (TOPK), which in turn led to activation of p53 pathway. Our findings supported GCM as a novel active compound that contributed to the anti-cancer activity of licorice and TOPK could be an effective target for hepatocellular carcinoma (HCC) treatment.

• Authors: Xinhua Song, Shutao Yin, Enxiang Zhang, Lihong Fan, Min Ye, Yong Zhang, Hongbo Hu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 40 Pg. 65732-65743 (Oct 04 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27582549 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Coumarins
• TP53 protein, human
• Tumor Suppressor Protein p53
• glycycoumarin
• Mitogen-Activated Protein Kinase Kinases
• PDZ-binding kinase

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Biomarkers, Tumor (metabolism)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Proliferation (drug effects)
• Coumarins (pharmacology)
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, chemistry, metabolism)
• Phosphorylation (drug effects)
• Protein Conformation (drug effects)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays