In Vitro and in Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis

Francisco Reigosa-Chamorro, Luís R. Raposo, Paula Munín-Cruz, M. Teresa Pereira, Catarina Roma-Rodrigues, Pedro V. Baptista, Alexandra R. Fernandes, José M. Vila

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3939-3951
Number of pages13
JournalInorganic Chemistry
Volume60
Issue number6
DOIs
Publication statusPublished - 15 Mar 2021

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