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31.07.2018

Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them

verfasst von: Zhijun Guo, Veronica Johnson, Jaime Barrera, Mariel Porras, Diego Hinojosa, Irwin Hernández, Patrick McGarrah, David A. Potter

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 2-3/2018

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Abstract

While cytochrome P450 (CYP)-mediated biosynthesis of arachidonic acid (AA) epoxides promotes tumor growth by driving angiogenesis, cancer cell intrinsic functions of CYPs are less understood. CYP-derived AA epoxides, called epoxyeicosatrienoic acids (EETs), also promote the growth of tumor epithelia. In cancer cells, CYP AA epoxygenase enzymes are associated with STAT3 and mTOR signaling, but also localize in mitochondria, where they promote the electron transport chain (ETC). Recently, the diabetes drug metformin was found to inhibit CYP AA epoxygenase activity, allowing the design of more potent biguanides to target tumor growth. Biguanide inhibition of EET synthesis suppresses STAT3 and mTOR pathways, as well as the ETC. Convergence of biguanide activity and eicosanoid biology in cancer has shown a new pathway to attack cancer metabolism and provides hope for improved treatments that target this vulnerability. Inhibition of EET-mediated cancer metabolism and angiogenesis therefore provides a dual approach for targeted cancer therapeutics.

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Titel: Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them
verfasst von: Zhijun Guo
Veronica Johnson
Jaime Barrera
Mariel Porras
Diego Hinojosa
Irwin Hernández
Patrick McGarrah
David A. Potter
Publikationsdatum: 31.07.2018
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 2-3/2018
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-018-9749-6

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Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them

Abstract

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

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