In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines
Autor: | Bojan Đ. Božić, Goran N. Kaluđerović, Nebojša Banjac, Ludger A. Wessjohann, Nebojša Pantelić, Bojana B. Zmejkovski, Biljana Dojčinović |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Cytotoxicity
Pharmaceutical Science Organic chemistry Apoptosis triphenyltin(IV) Ligands 01 natural sciences Mass Spectrometry Analytical Chemistry chemistry.chemical_compound Mice QD241-441 Breast cancer Neoplasms Drug Discovery Organotin Compounds Caspase biology Chemistry apoptosis Triphenyltin(IV) Reactive Nitrogen Species 3. Good health Chemistry (miscellaneous) Metals MCF-7 Cells Molecular Medicine cytotoxicity Female medicine.symptom HT29 Cells Caspase 3 In Vitro Techniques 010402 general chemistry Article Inhibitory Concentration 50 breast cancer Cell Line Tumor medicine ICP-MS Animals Humans Physical and Theoretical Chemistry 010405 organic chemistry Molecular biology In vitro 0104 chemical sciences Propanoic acid Mechanism of action Cell culture biology.protein NIH 3T3 Cells Gentian Violet Drug Screening Assays Antitumor Reactive Oxygen Species HeLa Cells |
Zdroj: | Molecules Molecules, Vol 26, Iss 3199, p 3199 (2021) Volume 26 Issue 11 |
ISSN: | 1420-3049 |
Popis: | The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells. |
Databáze: | OpenAIRE |
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