Novel pyridine-based chalcone analogs and triple negative breast cancer: potential therapy & molecular pathways

Area of Science:

• Oncology
• Medicinal Chemistry
• Molecular Pharmacology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited treatment options.
• Chalcone derivatives are recognized for their versatile anticancer properties and multitarget potential.
• There is an urgent need for novel therapeutic strategies to overcome TNBC resistance.

Purpose of the Study:

• To evaluate the anticancer efficacy of novel pyridine-based chalcone analogs against TNBC.
• To investigate the underlying molecular mechanisms of action for promising compounds.
• To assess the potential of these chalcones as next-generation TNBC therapeutics.

Main Methods:

• Screening of 14 pyridine-based chalcone analogs against TNBC cell lines (MDA-MB-231, BT-20).
• Assessment of cell viability, apoptosis (Annexin V/PI staining, cell cycle analysis), and invasion.
• Molecular analysis of apoptosis-related proteins (BAX) and signaling pathways (ERK1/2, EGFR).

Main Results:

• Two analogs, OH17 and OH25, demonstrated significant TNBC cell viability reduction at low micromolar concentrations.
• Both compounds induced apoptosis and cell cycle arrest, upregulated BAX, and downregulated ERK1/2.
• OH17 also modulated EGFR, and both compounds inhibited cell invasion and colony formation.

Conclusions:

• OH17 and OH25 exhibit potent anticancer activity against TNBC through distinct mechanisms, including apoptosis induction and invasion inhibition.
• These pyridine chalcones demonstrate significant potential to suppress key TNBC aggressiveness hallmarks.
• Further preclinical evaluation of OH17 and OH25 is warranted for developing novel TNBC therapies.