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.

中文翻译：

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硫代氨基脲-金属配合物通过氧化应激在结肠癌细胞系中表现出细胞毒性。

大肠癌是第三大常见癌症，在发达国家中发病率很高。目前，需要具体治疗以允许个体化治疗，这取决于药物可能作用的分子改变。该项目的目的是评估HPTSC和HPTSC *硫代半氨基甲酮（HPTSC =吡啶-2-甲氧基硫代半碳酮和HPTSC * =吡啶-2-甲醛4N-甲基硫代半碳酮）以及它们与不同过渡金属离子作为Cu（II）的配合物Fe（III）和Co（III）在具有不同致癌特性的结肠癌细胞（HT-29和SW-480）中具有抗肿瘤活性。评估了细胞毒性，并通过量化超氧化物歧化酶活性来分析氧化应激在其作用机理中的参与，通过量化硫氧还蛋白水平来降低氧化还原状态，降低/氧化谷胱甘肽的速率和生物分子的损害。通过测量胱天蛋白酶9和3的水平以及组蛋白的指数来评估凋亡作用。所有的金属硫代半氨基甲酮都具有抗氧化活性，该活性是由氧化应激介导的。HPTSC * -Cu是对KRAS基因突变的细胞系SW480表现出最佳抗肿瘤和凋亡特性的化合物。