Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria

The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport cha...

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Veröffentlicht in:	Cell chemical biology 2017-10, Vol.24 (10), p.1259-1275.e6
Hauptverfasser:	Guo, Zhijun, Sevrioukova, Irina F., Denisov, Ilia G., Zhang, Xia, Chiu, Ting-Lan, Thomas, Dafydd G., Hanse, Eric A., Cuellar, Rebecca A.D., Grinkova, Yelena V., Langenfeld, Vanessa Wankhede, Swedien, Daniel S., Stamschror, Justin D., Alvarez, Juan, Luna, Fernando, Galván, Adela, Bae, Young Kyung, Wulfkuhle, Julia D., Gallagher, Rosa I., Petricoin, Emanuel F., Norris, Beverly, Flory, Craig M., Schumacher, Robert J., O'Sullivan, M. Gerard, Cao, Qing, Chu, Haitao, Lipscomb, John D., Atkins, William M., Gupta, Kalpna, Kelekar, Ameeta, Blair, Ian A., Capdevila, Jorge H., Falck, John R., Sligar, Stephen G., Poulos, Thomas L., Georg, Gunda I., Ambrose, Elizabeth, Potter, David A.
Format:	Artikel
Sprache:	eng
Schlagworte:	AMP-Activated Protein Kinases - metabolism Animals autophagy biguanide Biguanides - chemistry Biguanides - metabolism Biguanides - pharmacology breast cancer Breast Neoplasms - pathology Catalytic Domain Cell Respiration - drug effects CYP3A4 Cytochrome P-450 CYP3A - chemistry Cytochrome P-450 CYP3A - deficiency Cytochrome P-450 CYP3A - genetics Cytochrome P-450 CYP3A - metabolism cytochrome P450 electron transport chain epoxyeicosatrienoic acid Estrogen Receptor alpha - genetics Female Gene Expression Regulation, Neoplastic - drug effects Gene Silencing Heme - metabolism hexyl-benzyl-biguanide Humans MCF-7 Cells Membrane Potential, Mitochondrial - drug effects metformin Mice mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondria - pathology Models, Molecular Protein Transport - drug effects
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