Impact of a Palladium(II)-tris(2-carboxyethyl)phosphine Complex on Normal Cells: Toxicity and Membrane Interaction

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Feb 13

PMID 39942580

Authors

Hanna Pruchnik

Katarzyna Solarska-Sciuk

Anita Dudek

Aleksandra Wloch

Affiliations

Soon will be listed here.

Abstract

Palladium(II) complexes with tris(2-carboxyethyl)phosphine (PdTCEP) show promise for biomedical applications due to their distinct chemical characteristics. This study explored the toxicity of PdTCEP towards normal human cells and examined its interactions with model cell membranes. Two cell types were used to evaluate cytotoxicity: human microvascular endothelial cells (HMEC-1) and red blood cells (RBCs). In HMEC-1 cells, PdTCEP reduced survival to about 80% at 15 µM, with the most significant drop-down to 40%-occurring at 40 µM. The production of reactive oxygen species (ROS) increased in a manner dependent on both dose and time, especially after 72 h of incubation. Despite these effects, PdTCEP caused only minor hemolysis in RBCs, with hemolysis levels staying below 10% even at higher concentrations. Fluorescence anisotropy measurements showed that PdTCEP minimally affects the hydrophobic core of the lipid bilayer, with slight changes observed at concentrations above 40 µM. Generalized polarization (GP) analysis indicated a slight decrease in lipid polar head packing with increasing PdTCEP concentration. Complementary FTIR analysis supported these findings by providing detailed insights into PdTCEP-membrane interactions. This research underscores PdTCEP's selective cytotoxicity and structural effects on membranes, suggesting its promise for more in-depth biological and pharmacological studies.

References

Henklewska M, Pawlak A, Kutkowska J, Pruchnik H, Rapak A, Obminska-Mrukowicz B . In vitro effects of the activity of novel platinum (II) complex in canine and human cell lines. Vet Comp Oncol. 2019; 17(4):497-506. DOI: 10.1111/vco.12511. View

Kenny R, Marmion C . Toward Multi-Targeted Platinum and Ruthenium Drugs-A New Paradigm in Cancer Drug Treatment Regimens?. Chem Rev. 2019; 119(2):1058-1137. DOI: 10.1021/acs.chemrev.8b00271. View

Alves A, Ribeiro D, Nunes C, Reis S . Biophysics in cancer: The relevance of drug-membrane interaction studies. Biochim Biophys Acta. 2016; 1858(9):2231-2244. DOI: 10.1016/j.bbamem.2016.06.025. View

Strugala P, Dudra A, Gabrielska J . Interaction between Mimic Lipid Membranes and Acylated and Nonacylated Cyanidin and Its Bioactivity. J Agric Food Chem. 2016; 64(39):7414-7422. DOI: 10.1021/acs.jafc.6b03066. View

Bourgaux C, Couvreur P . Interactions of anticancer drugs with biomembranes: what can we learn from model membranes?. J Control Release. 2014; 190:127-38. DOI: 10.1016/j.jconrel.2014.05.012. View

Suwalsky M, Duguet J, Speisky H . An In Vitro Study of the Antioxidant and Antihemolytic Properties of Buddleja globosa (Matico). J Membr Biol. 2017; 250(3):239-248. DOI: 10.1007/s00232-017-9955-0. View

Suwalsky M, Oyarce K, Avello M, Villena F, Sotomayor C . Human erythrocytes and molecular models of cell membranes are affected in vitro by Balbisia peduncularis (Amancay) extracts. Chem Biol Interact. 2009; 179(2-3):413-8. DOI: 10.1016/j.cbi.2008.12.011. View

Enriquez Garcia A, Jalilehvand F . Aerobic reactions of antitumor active dirhodium(II) tetraacetate Rh(CHCOO) with glutathione. J Biol Inorg Chem. 2017; 23(2):231-239. PMC: 5816706. DOI: 10.1007/s00775-017-1524-6. View

Jensen M, Nerdal W . Anticancer cisplatin interactions with bilayers of total lipid extract from pig brain: A13C, 31P and 15N solid-state NMR study. Eur J Pharm Sci. 2008; 34(2-3):140-8. DOI: 10.1016/j.ejps.2008.03.002. View

10.

Suwalsky M, Castillo I, Sanchez-Eguia B, Gallardo M, Dukes N, Santiago-Osorio E . In vitro effects of benzimidazole/thioether-copper complexes with antitumor activity on human erythrocytes. J Inorg Biochem. 2017; 178:87-93. DOI: 10.1016/j.jinorgbio.2017.10.009. View

11.

Maddy A, Dunn M, Kelly P . The characterisation of membrane proteins by centrifugation and gel electrophoresis. A comparison of proteins prepared by different methods. Biochim Biophys Acta. 1972; 288(2):263-76. DOI: 10.1016/0005-2736(72)90247-7. View

12.

Suwalsky M, Avello M . Antioxidant capacity of Ugni molinae fruit extract on human erythrocytes: an in vitro study. J Membr Biol. 2014; 247(8):703-12. DOI: 10.1007/s00232-014-9692-6. View

13.

Ndagi U, Mhlongo N, Soliman M . Metal complexes in cancer therapy - an update from drug design perspective. Drug Des Devel Ther. 2017; 11:599-616. PMC: 5344412. DOI: 10.2147/DDDT.S119488. View

14.

Englinger B, Pirker C, Heffeter P, Terenzi A, Kowol C, Keppler B . Metal Drugs and the Anticancer Immune Response. Chem Rev. 2018; 119(2):1519-1624. DOI: 10.1021/acs.chemrev.8b00396. View

15.

Wootton C, Millett A, Lopez-Clavijo A, Chiu C, Barrow M, Clarkson G . Structural analysis of peptides modified with organo-iridium complexes, opportunities from multi-mode fragmentation. Analyst. 2019; 144(5):1575-1581. DOI: 10.1039/c8an02094a. View

16.

Wang W, Zeng C, Feng Y, Zhou F, Liao F, Liu Y . The size-dependent effects of silica nanoparticles on endothelial cell apoptosis through activating the p53-caspase pathway. Environ Pollut. 2017; 233:218-225. DOI: 10.1016/j.envpol.2017.10.053. View

17.

Zhu D, Wang Z, Zong S, Zhang Y, Chen C, Zhang R . Investigating the Intracellular Behaviors of Liposomal Nanohybrids SERS: Insights into the Influence of Metal Nanoparticles. Theranostics. 2018; 8(4):941-954. PMC: 5817103. DOI: 10.7150/thno.21173. View

18.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

19.

Pruchnik H, Kral T, Hof M . Interaction of Newly Platinum(II) with Tris(2-carboxyethyl)phosphine Complex with DNA and Model Lipid Membrane. J Membr Biol. 2017; 250(5):461-470. PMC: 5613069. DOI: 10.1007/s00232-017-9972-z. View

20.

Bray F, Jemal A, Grey N, Ferlay J, Forman D . Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012; 13(8):790-801. DOI: 10.1016/S1470-2045(12)70211-5. View