Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and limited treatment options.
• Tiliroside (TS), a compound from Tribulus terrestris L., is explored for its therapeutic potential in TNBC.
• Carbonic anhydrase XII (CAXII) is implicated in TNBC progression and patient survival.

Purpose of the Study:

• To investigate the therapeutic efficacy of Tiliroside (TS) in triple-negative breast cancer (TNBC).
• To evaluate TS as a potential inhibitor of Carbonic anhydrase XII (CAXII) in TNBC.
• To explore the association between CAXII expression and TNBC patient survival.

Main Methods:

• Analysis of publicly accessible databases for CAXII expression and TNBC patient survival.
• In vitro assays: cell proliferation, wound healing, invasion, and 3D spheroid formation.
• In vivo mouse models, CAXII activity assays, pH measurements, lactate levels, RT-PCR, and Caspase-3 activity analysis.

Main Results:

• TS demonstrated significant anticancer activities in vitro, inhibiting TNBC cell proliferation, migration, and invasion.
• TS treatment reduced tumor burden and improved survival rates in mouse models of TNBC.
• TS was identified as a novel CAXII inhibitor, modulating cellular pH and lactate levels, and positively regulating the E2F1,3/Caspase-3 axis.

Conclusions:

• Tiliroside (TS) exhibits potent preclinical anticancer efficacy against triple-negative breast cancer (TNBC).
• TS functions as a novel CAXII inhibitor, suppressing TNBC progression.
• TS warrants further investigation for its therapeutic implications in TNBC treatment.