Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Oncology

Background:

• Ovarian cancer is a major cause of cancer mortality in women globally.
• Platinum-based chemotherapy is standard but faces resistance.
• Ruthenium(II) complexes are explored as novel anticancer agents.

Purpose of the Study:

• To evaluate the cytotoxic potential of three novel Ruthenium(II)-phosphine-mercapto complexes against ovarian cancer cells.
• To investigate the mechanism of action and selectivity of the most promising compound.
• To assess efficacy in 3D tumor spheroid models.

Main Methods:

• Synthesis and characterization of Ru(II) complexes.
• In vitro cytotoxicity assays on A2780 and A2780-cisR cells.
• 3D tumor spheroid assays.
• Cell cycle analysis, mitochondrial membrane potential assessment, and flow cytometry for apoptosis detection.
• Western blotting for key protein expression analysis (p53, PCNA, γH2AX, cleaved caspase-3).

Main Results:

• Compound 2 exhibited time-dependent cytotoxicity against ovarian cancer cells with better selectivity than cisplatin.
• Similar efficacy was observed in 3D tumor spheroids.
• Compound 2 induced apoptosis via mitochondrial pathway disruption without altering cell cycle distribution.
• Modulation of p53, PCNA, γH2AX, and cleaved caspase-3 expression was observed.

Conclusions:

• Ruthenium(II) complex 2 is a promising candidate for ovarian cancer therapy.
• Its mechanism involves inducing apoptosis and modulating key cellular pathways.
• Further investigation is warranted for its clinical application as an anticancer agent.