1. In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis.
- Author
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Reigosa-Chamorro F, Raposo LR, Munín-Cruz P, Pereira MT, Roma-Rodrigues C, Baptista PV, Fernandes AR, and Vila JM
- Subjects
- Angiogenesis Inhibitors chemical synthesis, Animals, Apoptosis drug effects, Autophagy drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Chickens, Coordination Complexes chemical synthesis, Embryo, Nonmammalian drug effects, Female, Fibroblasts drug effects, G1 Phase Cell Cycle Checkpoints drug effects, Humans, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Organometallic Compounds chemical synthesis, Ovarian Neoplasms drug therapy, Palladium chemistry, Reactive Oxygen Species metabolism, Angiogenesis Inhibitors pharmacology, Coordination Complexes pharmacology, Organometallic Compounds pharmacology
- Abstract
Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts. The compounds displayed selective cytotoxicity toward the A2780 cell line. Compound 3 decreased the cell viability through cell cycle retention in G0/G1, triggered apoptosis through the intrinsic pathway, and induced autophagy in A2780 cells. Compound 9 also induced cell cycle retention, apoptosis, and cellular detachment. Notably, compound 9 induced the production of intracellular reactive oxygen species (ROS). Our work demonstrated that compound 3 enters A2780 cells via active transport, which requires energy, while compound 9 enters A2780 cells mostly passively. The potential effect of palladacycles in angiogenesis was investigated for the first time in an in vivo chorioallantoic membrane model, showing that while compound 3 displayed an antiangiogenic effect crucial to fighting cancer progression, compound 9 promoted angiogenesis. These results show that palladacycles may be used in different clinical applications where pro- or antiangiogenic effects may be desirable.
- Published
- 2021
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