Thiosemicarbazone-metal complexes exhibiting cytotoxicity in colon cancer cell lines through oxidative stress

被引:21
作者
Alcaraz, Raquel [1 ]
Muniz, Pilar [2 ]
Cavia, Monica [2 ]
Palacios, Oscar [3 ]
Samper, Katia G. [3 ]
Gil-Garcia, Ruben [4 ]
Jimenez-Perez, Alondra [4 ]
Garcia-Tojal, Javier [4 ]
Garcia-Giron, Carlos [5 ]
机构
[1] Hosp Univ Burgos, Unidad Invest, Avd Islas Baleares 3, Burgos 09006, Spain
[2] Univ Burgos, Dept Biotecnol & Ciencia Alimentos, Plaza Misael Banuelos S-N, Burgos 09001, Spain
[3] Univ Autonoma Barcelona, Dept Quim, E-08193 Barcelona, Spain
[4] Univ Burgos, Dept Quim, Burgos 09001, Spain
[5] Hosp Univ Burgos, Serv Oncol Med, Avd Islas Baleares 3, Burgos 09006, Spain
关键词
Cell death; Cobalt compounds; Colon carcinoma; Iron compounds; Oxidative stress; Thiosemicarbazone; MONOTHIOSEMICARBAZONATO COPPER-II; DELOCALIZED SULFUR LIGANDS; IRON(III) COMPLEXES; COLORECTAL-CANCER; 2-FORMYLPYRIDINE THIOSEMICARBAZONE; ANTICANCER THIOSEMICARBAZONES; ANTIPROLIFERATIVE ACTIVITY; RIBONUCLEOTIDE REDUCTASE; BIOLOGICAL-ACTIVITY; CRYSTAL-STRUCTURE;
D O I
10.1016/j.jinorgbio.2020.110993
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:11
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