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Evaluation of the Antitumor Effects of Platinum-Based [Pt(η1-C2H4-OR)(DMSO)(phen)]+ (R = Me, Et) Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines

Authors :
Erika Stefàno
Luca Giulio Cossa
Federica De Castro
Erik De Luca
Viviana Vergaro
Giulia My
Gianluca Rovito
Danilo Migoni
Antonella Muscella
Santo Marsigliante
Michele Benedetti
Francesco Paolo Fanizzi
Source :
Bioinorganic Chemistry and Applications, Vol 2023 (2023)
Publication Year :
2023
Publisher :
Hindawi Limited, 2023.

Abstract

Pancreatic cancer is one of the most lethal malignancies with an increasing incidence and a high mortality rate, due to its rapid progression, invasiveness, and resistance to anticancer therapies. In this work, we evaluated the antiproliferative and antimigratory activities of the two organometallic compounds, [Pt(η1-C2H4-OMe)(DMSO)(phen)]Cl (1) and [Pt(η1-C2H4-OEt)(DMSO)(phen)]Cl (2), on three human pancreatic ductal adenocarcinoma cell lines with different sensitivity to cisplatin (Mia PaCa-2, PANC-1, and YAPC). The two cationic analogues showed superimposable antiproliferative effects on the tested cells, without significant differences depending on alkyl chain length (Me or Et). On the other hand, they demonstrated to be more effective than cisplatin, especially on YAPC cancer cells. For the interesting cytotoxic activity observed on YAPC, further biological assays were performed, on this cancer cell line, to evaluate the apoptotic and antimetastatic properties of the considered platinum compounds (1 and 2). The cytotoxicity of 1 and 2 compounds appeared to be related to their intracellular accumulation, which was much faster than that of cisplatin. Both 1 and 2 compounds significantly induced apoptosis and cell cycle arrest, with a high accumulation of sub-G1 phase cells, compared to cisplatin. Moreover, phenanthroline-containing complexes caused a rapid loss of mitochondria membrane potential, ΔΨM, if compared to cisplatin, probably due to their cationic and lipophilic properties. On 3D tumor spheroids, 1 and 2 significantly reduced migrated area more than cisplatin, confirming an antimetastatic ability.

Details

Language :
English
ISSN :
1687479X
Volume :
2023
Database :
Directory of Open Access Journals
Journal :
Bioinorganic Chemistry and Applications
Publication Type :
Academic Journal
Accession number :
edsdoj.fadec96f187f4039b2864751a1445b05
Document Type :
article
Full Text :
https://doi.org/10.1155/2023/5564624