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Evaluation of the Antitumor Effects of Platinum-Based Pt Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines
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Evaluation of the Antitumor Effects of Platinum-Based Pt Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines
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Evaluation of the Antitumor Effects of Platinum-Based Pt Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines
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Journal Article
Evaluation of the Antitumor Effects of Platinum-Based Pt Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines
2023
Overview
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(η [sup.1]-C[sub.2]H[sub.4]-OMe)(DMSO)(phen)]Cl (1) and [Pt(η [sup.1]-C[sub.2]H[sub.4]-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, Δ Ψ [sub.M], 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.
Publisher
John Wiley & Sons, Inc,Hindawi Limited
