Reactive Oxygen Species Inducing Triazolylpyridine-Based Ru(II)/Ir(III) Complexes for Therapeutically Enhanced...

Area of Science:

• Inorganic Chemistry
• Cancer Biology
• Medicinal Chemistry

Background:

• Existing treatments for triple-negative breast cancer (TNBC) have limited effectiveness.
• Reactive oxygen species (ROS)-mediated cancer cell death is a promising strategy to overcome treatment limitations.

Purpose of the Study:

• To develop novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes as ROS inducers for TNBC treatment.
• To investigate the mechanism of action of these complexes in TNBC cells.

Main Methods:

• Synthesis of novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes.
• Treatment of TNBC cells and 3D spheroids with the developed complexes.
• Analysis of mitochondrial accumulation, ROS generation, DNA damage, cell cycle arrest, apoptosis markers (BAX, BCL-2, caspase 3/9, cytochrome c), and spheroid viability.

Main Results:

• The Ru(II) complex accumulated in mitochondria, induced ROS production, and caused mitochondrial dysfunction and oxidative DNA damage.
• The complex led to G2/M phase cell cycle arrest and apoptosis by upregulating BAX, downregulating BCL-2, activating caspase 3/9, and releasing cytochrome c.
• The specific complex JRu significantly reduced the integrity and viability of TNBC 3D spheroids.

Conclusions:

• Novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes are effective ROS inducers for TNBC.
• These complexes induce cancer cell death through mitochondrial-mediated apoptosis and cell cycle arrest.
• The JRu complex demonstrates potential as a therapeutic agent against TNBC, including in 3D spheroid models.