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Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A
Merve Erkisa Genel1, Kaan Adacan2, Selin Selvi3
1Istinye University, Molecular Cancer Research Center (ISUMKAM), Istanbul, Turkey; Istanbul Health and Technology University, Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.
Abstract:
Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.
Insights
A novel dinuclear palladium(II) complex shows significant anti-cancer effects against breast cancer cells. This compound induces apoptosis, inhibits metastasis, and suppresses angiogenesis, suggesting its potential for breast cancer treatment.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- Breast cancer management necessitates novel therapeutic compounds due to high mortality and morbidity.
- Multinuclear metal complexes are being explored for their DNA binding affinity and cytotoxic potential.
Purpose of the Study:
- To investigate the anti-growth and cytotoxic effects of a dinuclear Palladium(II) complex on human breast cancer cell lines (MCF-7 and MDA-MB-231).
- To evaluate the complex's impact on cancer cell metastasis and angiogenesis.
Main Methods:
- Cell viability assays, staining methods, flow cytometry, and immunoblotting were used to assess cytotoxicity and apoptosis.
- Colony formation, invasion, and migration assays were performed to evaluate anti-metastatic properties.
- The Chorioallantoic Membrane (CAM) assay was employed to assess anti-angiogenic effects.
Main Results:
- The dinuclear Pd(II) complex induced apoptosis in both MCF-7 and MDA-MB-231 cells, evidenced by increased caspase-3/7 levels and positive annexin V staining.
- Apoptosis was confirmed through altered TNFR1 and TRADD expression, caspase-8 cleavage, BCL-2 inactivation, and loss of mitochondrial membrane potential.
- The complex demonstrated anti-migration properties and significantly inhibited angiogenesis in the CAM assay.
Conclusions:
- The dinuclear Pd(II) complex exhibits potent anti-cancer properties, including induction of apoptosis, inhibition of metastasis, and anti-angiogenesis.
- These findings highlight the therapeutic potential of this dinuclear Pd(II) complex for breast cancer treatment.
- Further in vivo studies are warranted to validate its efficacy and safety for clinical application.
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