Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells

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 ins...

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Bibliographic Details
Published inACS chemical biology Vol. 11; no. 5; pp. 1305 - 1312
Main Authors Abrams, Rachel P, Carroll, William L, Woerpel, K. A
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 20.05.2016
Subjects
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Death - drug effects
Cell Line
Cell Line, Tumor
Humans
Models, Molecular
Neoplasms - drug therapy
Neoplasms - metabolism
Oxidative Stress - drug effects
Peroxides - chemistry
Peroxides - pharmacology
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Summary: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.
ISSN:1554-8929
1554-8937
DOI:10.1021/acschembio.5b00900