Therapeutic Suppression of Triple-Negative Breast Cancer via Pachymic Acid-Induced KIF18B Inhibition and Ferroptosis...

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options.
• Pachymic acid (PA), a triterpenoid, shows potential therapeutic effects against TNBC, but its molecular mechanisms require further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the anti-TNBC effects of Pachymic acid (PA).
• To evaluate the therapeutic potential of PA in vitro and in vivo models of TNBC.

Main Methods:

• In vitro assays assessed cell viability, proliferation, invasion, and migration.
• Ferroptosis was evaluated by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels.
• In vivo efficacy was analyzed using animal xenograft models, with gene expression confirmed via immunoblot, qPCR, and immunohistochemistry.

Main Results:

• PA demonstrated significant antiproliferative, anti-migratory, and anti-invasive effects on TNBC cells.
• PA treatment induced oxidative stress and triggered ferroptosis in TNBC cells.
• PA downregulated the expression of Kinesin family member 18B (KIF18B), which was found to be overexpressed in TNBC. Restoring KIF18B expression counteracted PA's therapeutic effects in vitro and in vivo.

Conclusions:

• Pachymic acid (PA) suppresses TNBC progression by inducing ferroptosis and inhibiting malignant phenotypes.
• The mechanism involves the downregulation of Kinesin family member 18B (KIF18B).
• PA shows promise as a novel therapeutic agent for TNBC treatment.