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Labile iron affects pharmacological ascorbate-induced toxicity in osteosarcoma cell lines.
Free Radical Research ( IF 3.6 ) Pub Date : 2020-06-24 , DOI: 10.1080/10715762.2020.1744577
Liangfu Zhou 1 , Lixiu Zhang 1 , Shenghang Wang 1 , Bin Zhao 1 , Huanhuan Lv 1, 2, 3 , Peng Shang 2, 3
Affiliation  

Vitamin C and iron are both important nutrients for humans and involved in several physiological processes. The biological activities of vitamin C and iron are based on their abilities to accept or donate electrons. Although vitamin C is well known as an excellent electron donor in physiological conditions, it also has pro-oxidant properties, especially with catalytic metal iron. Cancer cells have a higher iron requirement than normal cells, which allows pharmacological ascorbate to kill cancer cells selectively. In this study, we demonstrated that the levels of H2O2 in cells were significantly raised after treated with pharmacological ascorbate, and intracellular labile iron could increase pharmacological ascorbate-mediated oxidative stress by Fenton reaction. Catalytic metal iron plays opposite roles in and outside cells. Intracellular excess labile iron improved ascorbate-induced toxicity, while the excess labile iron in the medium abolished ascorbate-induced toxicity. Fe3+ and Fe2+ have the same effect on ascorbate-induced toxicity, but Fe3+ chelator deferoxamine (DFO) has a profound inhibition effect than Fe2+ chelator 2,2′-bipyridyl (BIP) on ascorbate-induced toxicity. The influence of intracellular labile iron and ascorbate on the ferritin expression may cause selective sensitivity in osteosarcoma cell lines on pharmacological ascorbate. High iron requirement of many cancer cells facilitates pharmacological ascorbate on cancer treatment. In addition, increasing iron content in tumour tissue may be effective strategies to improve the effects of pharmacological ascorbate.



中文翻译:

不稳定铁影响骨肉瘤细胞系中药理抗坏血酸盐诱导的毒性。

维生素C和铁都是人类重要的营养素,并参与一些生理过程。维生素C和铁的生物活性基于其接受或捐赠电子的能力。尽管众所周知,维生素C在生理条件下是出色的电子供体,但它也具有促氧化剂特性,尤其是催化金属铁。癌细胞比正常细胞具有更高的铁需求,这使得药理学抗坏血酸选择性杀死癌细胞。在这项研究中,我们证明了H 2 O 2的水平药理抗坏血酸处理后细胞中的细胞明显升高,并且细胞内不稳定铁可通过Fenton反应增加药理抗坏血酸介导的氧化应激。催化金属铁在电池内部和外部起相反的作用。细胞内过量的不稳定铁改善了抗坏血酸诱导的毒性,而培养基中过量的不稳定铁则消除了抗坏血酸诱导的毒性。Fe 3+和Fe 2+对抗坏血酸的毒性作用相同,但Fe 3+螯合剂去铁胺(DFO)比Fe 2+具有更深的抑制作用螯合剂2,2'-联吡啶(BIP)对抗坏血酸诱导的毒性作用。细胞内不稳定铁和抗坏血酸对铁蛋白表达的影响可能导致骨肉瘤细胞系对药理学抗坏血酸具有选择性敏感性。许多癌细胞对铁的高需求促进了药物抗坏血酸对癌症的治疗。另外,增加肿瘤组织中的铁含量可能是改善药理学抗坏血酸作用的有效策略。

更新日期:2020-06-24
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