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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >DNA Damage in Dihydroartemisinin-resistant Molt-4 Cells
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DNA Damage in Dihydroartemisinin-resistant Molt-4 Cells

机译：双氢青蒿素抗性Molt-4细胞的DNA损伤

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摘要

Artemisinin generates carbon-based free radicals when it reacts with iron, and induces molecular damage and apoptosis. Its toxicity is more selective toward cancer cells because cancer cells contain a higher level of intracellular free iron. Dihydroartemisinin (DHA), an analog of artemisinin, has selective cytotoxicity toward Molt-4 human lymphoblastoid cells. A major concern is whether cancer cells could develop resistance to DHA, thus limiting its therapeutic efficacy. We have developed a DHA-resistant Molt-4 cell line (RTN) and found out that these cells exhibited resistance to DHA but no significant cross-resistance to artemisinin-tagged holotransferrin (ART-TF), a synthetic artemisinin compound. In the present study, we investigated DNA damage induced by DHA and ART-TF in both Molt-4 and RTN cells using the comet assay. RTN cells exhibited a significantly lower level of basal and X-ray-induced DNA damage compared to Molt-4 cells. Both DHA and ART-TF induced DNA damage in Molt-4 cells, whereas DNA damage was induced in RTN cells by ART-TF, and not DHA. The result of this study shows that by the cell selection method, it is possible to generate a Molt-4 cell line which is not sensitive to DHA, but sensitive to ART-TF, as measured by DNA damage.
机译：青蒿素与铁反应时会生成基于碳的自由基，并诱导分子损伤和细胞凋亡。它对癌细胞的毒性更具选择性，因为癌细胞包含更高水平的细胞内游离铁。双氢青蒿素（DHA）是青蒿素的类似物，对Molt-4人淋巴母细胞具有选择性的细胞毒性。一个主要的问题是癌细胞是否会发展出对DHA的抗性，从而限制其治疗功效。我们已经开发了一种抗DHA的Molt-4细胞系（RTN），发现这些细胞对DHA表现出抗性，但对青蒿素标记的全运铁蛋白（ART-TF）（一种合成青蒿素化合物）没有明显的交叉抗性。在本研究中，我们使用彗星试验研究了DHA和ART-TF在Molt-4和RTN细胞中诱导的DNA损伤。与Molt-4细胞相比，RTN细胞显示出显着更低的基础和X射线诱导的DNA损伤水平。 DHA和ART-TF均可诱导Molt-4细胞中的DNA损伤，而RTN细胞则可通过ART-TF而非DHA诱导DNA损伤。该研究的结果表明，通过细胞选择方法，可以产生对DHA不敏感但对ART-TF敏感的Molt-4细胞系，这是通过DNA损伤测定的。

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