1. Evaluation of anticancer activity of novel platinum(II) bis(thiosemicarbazone) complex against breast cancer.
- Author
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Radomska D, Szewczyk-Roszczenko OK, Marciniec K, Książek M, Kusz J, Roszczenko P, Szymanowska A, Radomski D, Bielawski K, and Czarnomysy R
- Subjects
- Humans, Structure-Activity Relationship, Molecular Structure, Female, Dose-Response Relationship, Drug, Cell Line, Tumor, Organoplatinum Compounds pharmacology, Organoplatinum Compounds chemistry, Organoplatinum Compounds chemical synthesis, Coordination Complexes pharmacology, Coordination Complexes chemistry, Coordination Complexes chemical synthesis, Platinum chemistry, Platinum pharmacology, Autophagy drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Thiosemicarbazones pharmacology, Thiosemicarbazones chemistry, Thiosemicarbazones chemical synthesis, Drug Screening Assays, Antitumor, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Apoptosis drug effects, Cell Proliferation drug effects
- Abstract
The study aims to synthesize a novel bis(thiosemicarbazone) derivative based on platinum (thioPt) and evaluate its anticancer properties against MFC-7 and MDA-MB-231 breast cancer cells. A new platinum complex was synthesised by reacting K
2 PtCl4 with 2,2'-(1,2-diphenylethane-1,2-diylidene)bis(hydrazine-1-carbothioamide) in ethanol in the presence of K2 CO3 . In the obtained complex, the platinum atom is coordinated by a conjugated system = N-NC-S-The structures of the new compound were characterised using NMR spectroscopy, HR MS, IR, and X-ray structural analysis. The obtained results of the cytotoxicity assay indicate that compound thioPt had potent anticancer activity (MCF-7: 61.03 ± 3.57 µM, MDA-MB-231: 60.05 ± 5.40 µM) with less toxicity against normal MCF-10A breast epithelial cells, even compared to the reference compound (cisplatin). In addition, subsequent experiments found that thioPt induces apoptosis through both an extrinsic (↑caspase 8 activity) and intrinsic (↓ΔΨm ) pathway, which ultimately leads to an increase in active caspase 3/7 levels. The induction of autophagy and levels of proteins involved in this process (LC3A/B and Beclin-1) were examined in MCF-7 and MDA-MB-231 breast cancer cells exposed to tested compounds (thio, thioPt, cisPt) at a concentration of 50 µM for 24 h. Based on these results, it can be concluded that thio and thioPt do not significantly affect the autophagy process. This demonstrates their superiority over cisplatin, which can stimulate cancer cell survival through its effect on stimulation of autophagy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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