Biological Evaluation of a Rhodium(III) Bipyridylsulfonamide Complex: Effects on Mitochondrial Dynamics and Cytoskeletal Remodeling in Breast Cancer Cells

• Published in: Journal of medicinal chemistry 2024-12, Vol.67 (23), p.21364-21379
• Main Authors: Audzeyenka, Irena, Piwkowska, Agnieszka, Rogacka, Dorota, Makowski, Mariusz, Kowalik, Mateusz
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Female; Humans; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Dynamics - drug effects; Oxidative Phosphorylation - drug effects; Rhodium - chemistry; Rhodium - pharmacology; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/acs.jmedchem.4c02284

Rhodium­(III) complexes have gained attention for their anticancer potential. In this study, we investigated a rhodium­(III) bipyridylsulfonamide complex (2) and its ligand (L) for their effects on breast cancer (SKBr3) and noncancerous mammary cells (HB2). Both compounds significantly reduced oxidative phosphorylation (OXPHOS) and mitochondrial function in SKBr3 cells while sparing HB2 cells. Compound 2 also increased glycolysis in both lines, suggesting a metabolic shift. Mitochondrial size and shape were altered, particularly in SKBr3 cells. Additionally, both compounds reduced cancer cell migration by disrupting actin cytoskeleton organization and the Rac1/VASP signaling pathway. These findings suggest that the rhodium­(III) bipyridylsulfonamide complex selectively impairs mitochondrial dynamics and cell migration in cancer cells while sparing healthy cells, providing insight into its mechanism of action and toward its use as targeted anticancer therapy. This study lays the groundwork for future in vivo studies and further optimization of these metal-based therapeutics for clinical applications.