Tiliroside as a CAXII inhibitor suppresses liver cancer development and modulates E2Fs/Caspase-3 axis

Area of Science:

• Oncology
• Pharmacology
• Natural Products

Background:

• Liver cancer is a leading cause of cancer mortality globally, characterized by aggressive behavior and limited treatment options.
• Tribulus terrestris L. is a medicinal herb used in traditional practices, containing the compound Tiliroside.
• The anti-cancer potential of Tiliroside, particularly against liver cancer, has not been previously investigated.

Purpose of the Study:

• To investigate the anti-cancer efficacy of Tiliroside against liver cancer cell lines.
• To explore the mechanism of action of Tiliroside, including its potential as a Carbonic anhydrase XII (CAXII) inhibitor.
• To assess the safety profile of Tiliroside on normal liver cells.

Main Methods:

• MTS assay for cell proliferation assessment.
• Colony formation, migration, and invasion assays to evaluate anti-cancer effects.
• 3D spheroid formation and CD133 expression analysis for anti-stemness properties.
• Biochemical assays (CAXII esterase activity, ELISA, RT-qPCR, CaspACE Assay) to investigate the CAXII inhibition and apoptotic pathway modulation.

Main Results:

• Tiliroside demonstrated significant anti-proliferation activity against liver cancer cell lines (Hep3B, SNU-449) with minimal toxicity to normal liver cells (THLE-3).
• Tiliroside exhibited anti-stemness effects, as evidenced by reduced 3D spheroid formation and CD133 expression.
• Evidence suggests Tiliroside functions as a Carbonic anhydrase XII (CAXII) inhibitor, impacting the apoptotic E2F1/E2F3/Caspase-3 signaling pathway.

Conclusions:

• Tiliroside possesses significant anti-liver cancer properties, including anti-proliferation and anti-stemness effects.
• Tiliroside acts as a novel Carbonic anhydrase XII (CAXII) inhibitor, offering a potential new therapeutic strategy for liver cancer.
• Further research into Tiliroside's therapeutic implications for liver cancer is warranted.