Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 206, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2020.110993
Keywords
Cell death; Cobalt compounds; Colon carcinoma; Iron compounds; Oxidative stress; Thiosemicarbazone
Funding
- Obra Social la Caixa [OSLC-2012-007]
- Gerencia Regional de Salud, Consejeria de Sanidad, Junta de Castilla y Leon [GRS 1023/A/14]
- Consejeria de Educacion, Junta de Castilla y Leon
- FEDER [BIO2015-67358-C2-2-P, 2017SGR-864, BU291P18, BU022G18]
- Ministerio de Economia y Competitividad [CTQ2016-75023-C2-1-P]
- MultiMetDrugs Network (Spain) [CTQ(QMC)-RED2018-102471-T]
- Spanish Ministerio de Ciencia e Innovacion
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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.
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