Bialystok University of Technology, Faculty of Civil Engineering and Environmental Engineering, Division of Chemistry, Biology and Biotechnology, Wiejska 45E, 15-351, Bialystok, Poland.
Bialystok University of Technology, Faculty of Civil Engineering and Environmental Engineering, Division of Chemistry, Biology and Biotechnology, Wiejska 45E, 15-351, Bialystok, Poland.
J Trace Elem Med Biol. 2018 Jul;48:141-148. doi: 10.1016/j.jtemb.2018.03.021. Epub 2018 Mar 26.
The most important problems of anti-cancer therapy include the toxicity of the drugs applied to healthy cells and the multi-drug cells resistance to chemotherapeutics. One of the most commonly used anticancer drugs is doxorubicin (DOX) used to treat certain leukemias and non-Hodgkin's lymphomas, as well as bladder, breast, stomach, lung, ovarian, thyroid, multiple myeloma and other cancers. Preliminary studies showed that metal complex with DOX improve its cytostatic activity with changes in their molecular structure and distribution of electrons, resulting in a substantial change of its biological activity (including antitumor activity). Thus, there is a chance to receiving derivatives of DOX with low toxicity for the healthy body cells, thus increasing its therapeutic selectivity. In the present study we examined the influence of Mn, Mg, Fe, Co and Ni, seleno-l-methionine and vitamin C on biological activity of DOX in prokaryotic model - Escherichia coli RFM443, with plasmid transcriptional fusion of recA promoter and luxCDABE as a reporter gene. Cytotoxic potency of tested chemicals was calculated on the basis of the bacteria culture growth inhibition (GI%) values. Genotoxic properties were calculated on the basis of the fold increase (FI) of relative luminescence units (RLU) values compared to control. Obtained results showed that doxorubicin metal complexes particularly with Ni, Co and Fe increased the cyto- and genotoxic activities of DOX. Bacteria culture supplemented with SeMet and vitamin C differentiate the DOX and its metal complexes toxicity. It seems, that DOX-Ni, DOX-Fe and DOX-Co complexes could be potent cytostatic drug candidates. Moreover, we noticed different sensitivity of recA::luxCDABE for 3 h and 24 h cultures of bacteria strain. It suggests, that the potency of genetic construct reactivity- recA::luxCDABE in E. coli depends on the growth-phase of bacterial culture.
抗癌治疗中最重要的问题包括应用于健康细胞的药物的毒性和多药细胞对化疗药物的耐药性。阿霉素（DOX）是最常用的抗癌药物之一，用于治疗某些白血病和非霍奇金淋巴瘤，以及膀胱癌、乳腺癌、胃癌、肺癌、卵巢癌、甲状腺癌、多发性骨髓瘤和其他癌症。初步研究表明，DOX 的金属配合物通过改变其分子结构和电子分布来提高其细胞抑制活性，从而导致其生物活性（包括抗肿瘤活性）发生实质性变化。因此，有可能获得对健康细胞毒性较低的 DOX 衍生物，从而提高其治疗选择性。在本研究中，我们研究了 Mn、Mg、Fe、Co 和 Ni、硒代蛋氨酸和维生素 C 对原核模型 - 大肠杆菌 RFM443 中 DOX 生物活性的影响，该模型使用 recA 启动子的转录融合和 luxCDABE 作为报告基因。基于细菌培养物生长抑制（GI%）值计算测试化学品的细胞毒性效力。基于与对照相比相对发光单位（RLU）值的倍数增加（FI）计算遗传毒性特性。结果表明，DOX 金属配合物特别是与 Ni、Co 和 Fe 一起，增加了 DOX 的细胞毒性和遗传毒性活性。添加 SeMet 和维生素 C 的细菌培养物可区分 DOX 及其金属配合物的毒性。似乎 DOX-Ni、DOX-Fe 和 DOX-Co 配合物可能是有效的细胞抑制剂候选物。此外，我们注意到 recA::luxCDABE 对细菌菌株 3 h 和 24 h 培养物的敏感性不同。这表明遗传构建体反应性 recA::luxCDABE 的效力取决于细菌培养物的生长阶段。
