关键词: 5-fluorouracil colon cancer electroporation frataxin iron(III) citrate iron(III)–EDTA nanosecond pulses

来  源:   DOI:10.3390/ph17050651   PDF(Pubmed)

Abstract:
Colon cancer (CC) management includes surgery, radio- and chemotherapy based on treatment with 5-fluorouracil (5-FU) or its derivatives. However, its application is limited to low-grade carcinomas. Thus, much research has been conducted to introduce new techniques and drugs to the therapy. CC mostly affects older people suffering from cardiac diseases, where iron compounds are commonly used. Ferric citrate and iron (III)-EDTA complexes have proven to be effective in colon cancer in vitro. This study aimed to determine the potency and action of iron-containing compounds in colon cancer treatment by chemo- and electrochemotherapy in both nano- and microsecond protocols. The viability of the cells was assessed after standalone iron (III) citrate and iron (III)-EDTA incubation. Both compounds were also assessed with 5-FU to determine the combination index. Additionally, frataxin expression was taken as the quantitative response to the exposition of iron compounds. Each of the substances exhibited a cytotoxic effect on the LoVo cell line. Electroporation with standalone drugs revealed the potency of 5-FU and iron(III)-EDTA in CC treatment. The combination of 5-FU with iron(III)-EDTA acted synergistically, increasing the viability of the cells in the nanosecond electrochemotherapy protocol. Iron(III)-EDTA decreased the frataxin expression, thus inducing ferroptosis. Iron(III) citrate induced the progression of cancer; therefore, it should not be considered as a potential therapeutic option. The relatively low stability of iron(III) citrate leads to the delivery of citrate anions to cancer cells, which could increase the Krebs cycle rate and promote progression.
摘要:
结肠癌(CC)管理包括手术,基于用5-氟尿嘧啶(5-FU)或其衍生物治疗的放疗和化疗。然而,它的应用仅限于低度癌。因此,已经进行了许多研究,以将新技术和药物引入该疗法。CC主要影响患有心脏病的老年人,其中铁化合物是常用的。柠檬酸铁和铁(III)-EDTA复合物已被证明在体外对结肠癌有效。这项研究旨在确定含铁化合物在纳米和微秒方案中通过化学和电化学疗法治疗结肠癌中的效力和作用。在单独的柠檬酸铁(III)和铁(III)-EDTA孵育后评估细胞的活力。还用5-FU评估两种化合物以确定组合指数。此外,共济失调素的表达被认为是对铁化合物暴露的定量反应。每种物质对LoVo细胞系表现出细胞毒性作用。用独立药物进行电穿孔显示5-FU和铁(III)-EDTA在CC治疗中的效力。5-FU与铁(III)-EDTA的组合协同作用,在纳秒电化疗方案中增加细胞的活力。铁(III)-EDTA降低共济失调蛋白表达,从而诱导铁性凋亡。柠檬酸铁(III)诱导癌症的进展;因此,不应将其视为潜在的治疗选择.柠檬酸铁(III)的相对较低的稳定性导致柠檬酸根阴离子向癌细胞递送,这可以提高克雷布斯周期率并促进进展。
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