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
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...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2023/5564624 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Erika Stefàno |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fadec96f187f4039b2864751a1445b05 |
| institution | Kabale University |
| issn | 1687-479X |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-fadec96f187f4039b2864751a1445b052025-02-03T06:43:15ZengWileyBioinorganic Chemistry and Applications1687-479X2023-01-01202310.1155/2023/5564624Evaluation of the Antitumor Effects of Platinum-Based [Pt(η1-C2H4-OR)(DMSO)(phen)]+ (R = Me, Et) Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell LinesErika Stefàno0Luca Giulio Cossa1Federica De Castro2Erik De Luca3Viviana Vergaro4Giulia My5Gianluca Rovito6Danilo Migoni7Antonella Muscella8Santo Marsigliante9Michele Benedetti10Francesco Paolo Fanizzi11Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)Department of Biological and Environmental Sciences and Technologies (DiSTeBA)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.http://dx.doi.org/10.1155/2023/5564624 |
| spellingShingle | 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 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 Bioinorganic Chemistry and Applications |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2023/5564624 |
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