Teroxirone suppresses growth and motility of human hepatocellular carcinoma cells.

Abstract

AIMS:

The prevalent human hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality. The small molecular weight triepoxide derivative, 1,3,5-triazine-2,4,6(1H,3H,5H)-tri-one-1,3,5-tri-(oxiranylmethyl) (teroxirone), has been proved effective against the proliferation of lung cancer cells. The purpose is to further examine if teroxirone regulate growth and metastatic potential of HCC cells with aims at disclosing more of the reaction mechanisms.

MAIN METHODS:

Measurements of cell viability and flow cytometry were conducted to test sensitivities of teroxirone against HCC cells. The signaling pathway leading to apoptotic death was unraveled by Western blotting analysis. The metastatic progression was evaluated by cell-based phenotype assay that included migration, invasion, gelatin zymography and wound assay. The in vivo drug efficiency was done in immune-deficient mice with the established xenograft tumors.

KEY FINDINGS:

Teroxirone inhibited growth of HCC cells, but not hepatic cells. The drug induced apoptosis in HCC cells bearing mutant p53. Pretreatment of caspase-3 inhibitor restored cell viabilities by suppressing extrinsic pathway-mediated cell death. More experiments suggested that sub-apoptotic concentrations of teroxirone mitigated migration, invasion and wound healing of HCC cells. The drug reduced growth of the xenograft tumors as established in animal models by activating apoptotic death.

SIGNIFICANCE:

The findings asserted that teroxirone is an eligible addition to the existing options as an anticancer agent to eliminate HCC.

• Authors: Seung-Hun Kim, Wen-Hsing Wang, Jing-Ping Wang, Chang-Heng Hsieh, Kang Fang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 99 Pg. 997-1008 (Mar 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29653488 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Caspase Inhibitors
• Triazines
• teroxirone
• Cytochromes c
• Caspase 3
• Matrix Metalloproteinases

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (pathology)
• Caspase 3 (metabolism)
• Caspase Inhibitors (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• Female
• Humans
• Liver Neoplasms (pathology)
• Matrix Metalloproteinases (metabolism)
• Mice, Nude
• Neoplasm Invasiveness
• Signal Transduction (drug effects)
• Triazines (pharmacology)
• Wound Healing (drug effects)
• Xenograft Model Antitumor Assays