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Fusaricide is a Novel Iron Chelator that Induces Apoptosis through Activating Caspase-3
Journal of Natural Products ( IF 3.3 ) Pub Date : 2021-07-22 , DOI: 10.1021/acs.jnatprod.0c01322
Yaling Hui 1 , Ting Tang 1 , Jing Wang 1 , Huanhuan Zhao 1 , Hong-Ying Yang 1 , Junmin Xi 1 , Baoxin Zhang 1 , Jianguo Fang 1 , Kun Gao 1 , Yueting Wu 1
Affiliation  

Nonsmall cell lung cancer (NSCLC) has been a fatal and refractory disease worldwide. Novel therapeutic developments based on fundamental investigations of anticancer mechanisms underlie substantial foundations to win the fight against cancer diseases. In this study, we isolated a natural product fusaricide (FCD) from an endophytic fungus of Lycium barbarum, identified as Epicoccum sp. For the first time, we discovered that FCD potently inhibited proliferation in a variety of human NSCLC cell lines, with relatively less toxicity to normal cells. Our study exhibited that FCD induced apoptosis, caused DNA damage and cell cycle arrest in G0/G1 phase, and activated caspase-3 as well as other apoptosis-related factors in human NSCLC NCI-H460 cells. FCD was proven to be an iron chelator that actively decreased levels of cellular labile iron pool in NCI-H460 cells in our study. FeCl3 supplement reversed FCD-induced apoptosis. The upregulation of transferrin receptor 1 (TfR1) and downregulation of ferritin heavy chain (FTH) expression were observed after FCD treatment. In summary, our study highlighted the potential anticancer effects of FCD against human NSCLCs and demonstrated that the FCD-mediated apoptosis depended on binding to intracellular iron.

中文翻译:

Fusaricide 是一种新型铁螯合剂,可通过激活 Caspase-3 诱导细胞凋亡

非小细胞肺癌 (NSCLC) 在世界范围内是一种致命且难治的疾病。基于抗癌机制的基础研究的新疗法发展奠定了战胜癌症疾病的坚实基础。在这项研究中,我们从枸杞内生真菌中分离出一种天然产物镰刀菌 (FCD) ,鉴定为Epicoccum sp. 我们首次发现 FCD 能有效抑制多种人类 NSCLC 细胞系的增殖,对正常细胞的毒性相对较小。我们的研究表明,FCD 诱导细胞凋亡,在 G0/G1 期引起 DNA 损伤和细胞周期停滞,并激活人非小细胞肺癌 NCI-H460 细胞中的 caspase-3 以及其他凋亡相关因子。在我们的研究中,FCD 被证明是一种铁螯合剂,可主动降低 NCI-H460 细胞中细胞不稳定铁库的水平。的FeCl 3补充逆转 FCD 诱导的细胞凋亡。在 FCD 治疗后观察到转铁蛋白受体 1 (TfR1) 上调和铁蛋白重链 (FTH) 表达下调。总之,我们的研究强调了 FCD 对人非小细胞肺癌的潜在抗癌作用,并证明 FCD 介导的细胞凋亡取决于与细胞内铁的结合。
更新日期:2021-08-27
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