Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation
Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation
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海洋真菌代谢物 (3S,6S)-3,6-二苄基哌嗪-2,5-二酮对适应营养饥饿的癌细胞的选择性细胞毒性
DOI：
10.1038/s41429-020-0340-3
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Arai Masayoshi
中科院分区：
文献类型：
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作者：
Tang Rui;Zhou Dongyi;Kimishima Atsushi;Setiawan Andi;Arai Masayoshi
适应肿瘤微环境低氧和营养匮乏条件的癌细胞已成为抗癌治疗的关键靶点。在寻找适应营养饥饿的选择性抗肿瘤细胞毒性物质的过程中，从海洋来源的拟青霉17D47-2的培养提取物中分离得到(3S，6S)-3，6-二苄基哌嗪-2，5-二酮(1)。化合物1对适应葡萄糖缺乏条件的人胰腺癌PANC-1细胞具有细胞毒作用，IC50值为28 µM，而在一般培养条件下对PANC-1细胞无明显作用。进一步研究化合物1对葡萄糖缺乏的PANC-1细胞的选择性细胞毒作用的机制表明，化合物1可能通过解偶联线粒体氧化磷酸化作用发挥作用。
The cancer cells that are adapted to the hypoxic and nutrient-starved conditions of the tumor microenvironment have become a key target for anticancer therapies. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, (3S,6S)-3,6-dibenzylpiperazine-2,5-dione (1) was isolated from culture extract of marine-derivedPaecilomyces formous17D47-2. Compound1showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC50value of 28 µM, whereas no effect was observed against PANC-1 cells under general culture conditions up to 1000 µM. Further studies on the mechanism of the selective cytotoxicity of1against the glucose-starved PANC-1 cells suggest that it may function via uncoupling of mitochondrial oxidative phosphorylation.