Citation:

In Vitro and in Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis, Reigosa-Chamorro, Francisco, Raposo {Luís R. }, Munín-Cruz Paula, Pereira Teresa} {M., Roma-Rodrigues Catarina, Baptista {Pedro V. }, Fernandes {Alexandra R. }, and Vila {José M. } , Inorganic Chemistry, mar, Volume 60, Number 6, p.3939–3951, (2021)

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.

Notes:

This work was financed by national funds from FCT through the Applied Molecular Biosciences Unit, UCIBIO (Grants UIDP/04378/2020 and UIDB/04378/2020), and fellowships SFRH/BPD/124612/2016 (to C.R.-R.) and PTDC/CVTEPI/6685/2014 (to L.R.R.). This work was also made possible thanks to financial support received from the Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme (Project GRC2019/14). F.R.-C. thanks the Spanish Ministry of Education (Grant FPU15/07145).