In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis
- 3 March 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Inorganic Chemistry
- Vol. 60 (6), 3939-3951
- https://doi.org/10.1021/acs.inorgchem.0c03763
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.Keywords
Funding Information
- Xunta de Galicia (GRC2019/14)
- Funda??o para a Ci?ncia e a Tecnologia (PTDC/CVT-EPI/6685/2014, SFRH/BPD/124612/2016, UIDB/04378/2020, UIDP/04378/2020)
- Spanish Ministry of Education (FPU15/07145)
This publication has 58 references indexed in Scilit:
- Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cellsBMC Cancer, 2013
- Electron-Rich Trialkyl-Type Dihydro-KITPHOS Monophosphines: Efficient Ligands for Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling. Comparison with Their Biaryl-Like KITPHOS Monophosphine CounterpartsOrganometallics, 2013
- Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side EffectsCancers, 2011
- Synthesis and Structural Characterization of New Bimetallic [C,N,S] Palladacycles with Mixed Bridging [P,P] and Chelating [P,P] or [P,N] Phosphane LigandsEuropean Journal of Inorganic Chemistry, 2010
- Synthesis, Characterization, and Catalytic Applications of Palladacyclic Complexes Bearing C,N,S‐Donor LigandsEuropean Journal of Inorganic Chemistry, 2006
- Long-Term Survival After Cisplatin-Based Induction Chemotherapy and Radiotherapy for Nasopharyngeal Carcinoma: A Pooled Data Analysis of Two Phase III TrialsJournal of Clinical Oncology, 2005
- Palladacyclic catalysts in C–C and C–heteroatom bond-forming reactionsChemical Communications, 2003
- Palladium-Catalyzed Coupling Reactions of Aryl ChloridesAngewandte Chemie, 2002
- Trypan Blue Exclusion Test of Cell ViabilityCurrent Protocols in Immunology, 1997
- Aromatic Metalation Reactions by Palladium(II) and Platinum(II) on Aromatic Aldoximes and KetoximesBulletin of the Chemical Society of Japan, 1970