Thiosemicarbazone-metal complexes exhibiting cytotoxicity in colon cancer cell lines through oxidative stress
| Autor: | Rubén Gil-García, Raquel Alcaraz, Alondra Jiménez-Pérez, Pilar Muñiz, Javier García-Tojal, Mónica Cavia, Katia G. Samper, Carlos García-Girón, Òscar Palacios |
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| Rok vydání: | 2020 |
| Předmět: |
Thiosemicarbazones
Cell death Bioquímica Programmed cell death Cell Survival Pyridines Colon carcinoma Antineoplastic Agents Apoptosis Iron compounds 010402 general chemistry medicine.disease_cause Ferric Compounds Thiosemicarbazone 01 natural sciences Biochemistry Inorganic Chemistry Coordination Complexes Cell Line Tumor Organometallic Compounds medicine Humans Cytotoxicity Caspase-9 Cobalt compounds Cell Death biology 010405 organic chemistry Chemistry Cancer Cobalt medicine.disease Glutathione 0104 chemical sciences Oxidative Stress Mechanism of action Oxidative stress Colonic Neoplasms biology.protein Cancer research Drug Screening Assays Antitumor medicine.symptom Thioredoxin HT29 Cells Oxidation-Reduction Copper |
| Zdroj: | Repositorio Institucional de la Universidad de Burgos (RIUBU) instname |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2020.110993 |
| Popis: | Colorectal cancer is the third most common type of cancer and has a high incidence in developed countries. At present, specific treatments are being required to allow individualized therapy depending on the molecular alteration on which the drug may act. The aim of this project is to evaluate whether HPTSC and HPTSC* thiosemicarbazones (HPTSC = pyridine-2-carbaldehyde thiosemicarbazone and HPTSC* = pyridine-2-carbaldehyde 4N-methylthiosemicarbazone), and their complexes with different transition metal ions as Cu(II), Fe(III) and Co(III), have antitumor activity in colon cancer cells (HT-29 and SW-480), that have different oncogenic characteristics. Cytotoxicity was evaluated and the involvement of oxidative stress in its mechanism of action was analyzed by quantifying the superoxide dismutase activity, redox state by quantification of the thioredoxin levels and reduced/oxidized glutathione rate and biomolecules damage. The apoptotic effect was evaluated by measurements of the levels of caspase 9 and 3 and the index of histones. All the metal-thiosemicarbazones have antitumor activity mediated by oxidative stress. The HPTSC*-Cu was the compound that showed the best antitumor and apoptotic characteristics for the cell line SW480, that is KRAS gene mutated. |
| Databáze: | OpenAIRE |
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