Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them
| Autor: | Mariel Porras, Irwin Hernandez, David Potter, Patrick W. McGarrah, Zhijun Guo, Diego Hinojosa, Veronica Johnson, Jaime Barrera |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epoxygenase Cancer Research Angiogenesis Antineoplastic Agents Epoxyeicosatrienoic acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System Neoplasms Drug Discovery Autophagy Tumor Microenvironment medicine Animals Cytochrome P-450 Enzyme Inhibitors Humans Drug Interactions Molecular Targeted Therapy PI3K/AKT/mTOR pathway Clinical Trials as Topic CYP3A4 biology Chemistry Drug Repositioning Cytochrome P450 Cancer medicine.disease Mitochondria Treatment Outcome 030104 developmental biology Electron Transport Chain Complex Proteins Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Signal Transduction |
| Zdroj: | Cancer and Metastasis Reviews. 37:409-423 |
| ISSN: | 1573-7233 0167-7659 |
| DOI: | 10.1007/s10555-018-9749-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink