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Selective Targeting of Regulated Rhabdomyosarcoma Cells by Trinuclear Ruthenium(II)-Arene Complexes
Athi Welsh1, Karabo Serala2, Sharon Prince2
1Department of Chemistry, University of Cape Town, Rondebosch, Cape Town 7700, South Africa.
Journal of Medicinal Chemistry
|April 3, 2024
Summary
New ruthenium complexes selectively target and kill rhabdomyosarcoma (RMS). Complex 1 shows superior cytotoxicity and inhibits metastasis in RMS cells, offering a promising new avenue for rare cancer treatment.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Inorganic Chemistry
Background:
- Rhabdomyosarcoma (RMS) is a rare cancer with limited treatment options.
- Ruthenium(II)-arene complexes are being investigated for their anticancer properties.
Purpose of the Study:
- To evaluate benzimidazole-based trinuclear ruthenium(II)-arene complexes for selective targeting of RMS.
- To investigate the efficacy and mechanism of action of these complexes against RMS cells.
Main Methods:
- Synthesis and characterization of trinuclear ruthenium(II)-arene complexes.
- In vitro cytotoxic evaluation across an eight-cancer cell line panel.
- Assessment of cell migration, 3D spheroid growth inhibition, and mechanistic studies (DNA damage, autophagy, apoptosis).
Main Results:
- Ruthenium complexes 1-3 demonstrated selective cytotoxicity toward RMS cells.
- Trinuclear complex 1 exhibited superior short- and long-term cytotoxicity and selectivity compared to cisplatin.
- Complex 1 inhibited RMS cell migration, showed enhanced activity in 3D spheroids, induced DNA damage, autophagy, and apoptosis.
Conclusions:
- Benzimidazole-based trinuclear ruthenium(II)-arene complex 1 is a potent and selective agent against rhabdomyosarcoma.
- Complex 1 offers a promising therapeutic strategy for RMS, demonstrating efficacy in preclinical models.
- This study presents the first trinuclear ruthenium(II) arene complex with selective RMS-killing capabilities in 2D and 3D cultures.
