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Erschienen in: Medical Oncology 9/2023

01.09.2023 | Original Paper

The Schiff base hydrazine copper(II) complexes induce apoptosis by P53 overexpression and prevent cell migration through protease-independent pathways

verfasst von: Vahid Asghariazar, Mohammad Amini, Zahra Pirdel, Roghayeh Fekri, Asadollah Asadi, Kazem Nejati-Koshki, Behzad Baradaran, Yasin Panahi

Erschienen in: Medical Oncology | Ausgabe 9/2023

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Abstract

Although chemotherapy has increased the life expectancy of cancer patients, its toxic side effects remain a major challenge. Recently, organometallic compounds, such as Schiff base copper complexes, have become promising candidates for next-generation anticancer drugs owing to their unique anticancer activities. In this study, binuclear copper(II) complex-1 and mononuclear copper(II) complex-2 were examined to analyze their anticancer mechanisms further. For this purpose, a viability test, flow cytometry analysis of apoptosis and the cell cycle, migration assay, and gene expression analysis were performed. According to our results, complex-1 was more cytotoxic than complex-2 at 24/48-h intervals. Our findings also demonstrated that both complexes induced apoptosis at IC50 concentrations and arrested the cell cycle at the G1-S checkpoint. However, complex-1 accelerates cell cycle arrest at the sub-G0/G1 phase more than complex-2 does. Furthermore, gene expression analysis showed that only complex-1 induces the expression of p53. Interestingly, both complexes induced Bcl-2 overexpression. However, they did not affect MMP-13 expression. More interestingly, both complexes inhibited cell migration in different ways, including amoeboid and collective, by recruiting protease-independent pathways. This study confirmed that adding several metal cores and co-ligands increased the activity of the complex. It also appeared that Cu-containing complexes could prevent the migration of cancer cells through protease-independent pathways, which can be used for novel therapeutic purposes.
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Metadaten
Titel
The Schiff base hydrazine copper(II) complexes induce apoptosis by P53 overexpression and prevent cell migration through protease-independent pathways
verfasst von
Vahid Asghariazar
Mohammad Amini
Zahra Pirdel
Roghayeh Fekri
Asadollah Asadi
Kazem Nejati-Koshki
Behzad Baradaran
Yasin Panahi
Publikationsdatum
01.09.2023
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 9/2023
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-023-02150-2

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