Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells.

Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells.
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DOI:
10.1021/acschembio.5b00900
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发表时间:
2016-05-20
影响因子:
4
通讯作者:
Woerpel KA
Woerpel KA
中科院分区:
生物学2区
文献类型:
--
作者:
Abrams RP;Carroll WL;Woerpel KA

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通过有机过氧化物筛选,将 1,2-二氧戊环 (FINO2) 鉴定为先导化合物。 FINO2 不会诱导细胞凋亡,而是引发铁死亡,这是一种铁依赖性氧化细胞死亡途径。已知很少有化合物能引起原发性铁死亡。与过氧化物的不稳定性相比,FINO2 在至少 150 °C 的温度下具有热稳定性。 FINO2 在癌细胞中比同类型的非恶性细胞更有效。发现其中一种对映体对观察到的活性负有更大的责任。
A 1,2-dioxolane (FINO2) was identified as a lead compound from a screen of organic peroxides. FINO2 does not induce apoptosis, but instead initiates ferroptosis, an iron-dependent, oxidative cell death pathway. Few compounds are known to induce primarily ferroptosis. In contrast to the perceived instability of peroxides, FINO2 was found to be thermally stable to at least 150 °C. FINO2 was more potent in cancer cells than nonmalignant cells of the same type. One of the enantiomers was found to be more responsible for the observed activity.
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