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Published in:

01-09-2018

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

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

Published in: Cancer and Metastasis Reviews | Issue 2-3/2018

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.

Panigrahy, D., Greene, E. R., Pozzi, A., Wang, D. W., & Zeldin, D. C. (2011). EET signaling in cancer. Cancer Metastasis Reviews, 30, 525–540. https://doi.org/10.1007/s10555-011-9315-y.PubMedPubMedCentralCrossRef

Capdevila, J., Chacos, N., Werringloer, J., Prough, R. A., & Estabrook, R. W. (1981). Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proceedings of the National Academy of Sciences of the United States of America, 78(9), 5362–5366.PubMedPubMedCentralCrossRef

Capdevila, J., Parkhill, L., Chacos, N., Okita, R., Masters, B. S., & Estabrook, R. W. (1981). The oxidative metabolism of arachidonic acid by purified cytochromes P-450. Biochemical and Biophysical Research Communications, 101(4), 1357–1363.PubMedCrossRef

Chacos, N., Falck, J. R., Wixtrom, C., & Capdevila, J. (1982). Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochemical and Biophysical Research Communications, 104(3), 916–922.PubMedCrossRef

Fleming, I. (2007). Epoxyeicosatrienoic acids, cell signaling and angiogenesis. Prostaglandins & Other Lipid Mediators, 82(1–4), 60–67.CrossRef

Fleming, I. (2008). Vascular cytochrome p450 enzymes: physiology and pathophysiology. Trends in Cardiovascular Medicine, 18(1), 20–25. https://doi.org/10.1016/j.tcm.2007.11.002.PubMedCrossRef

Fleming, I. (2011). The cytochrome P450 pathway in angiogenesis and endothelial cell biology. Cancer Metastasis Reviews, 30, 541–555. https://doi.org/10.1007/s10555-011-9302-3.PubMedCrossRef

Fleming, I. (2016). The factor in EDHF: cytochrome P450 derived lipid mediators and vascular signaling. Vascular Pharmacology, 86, 31–40. https://doi.org/10.1016/j.vph.2016.03.001.PubMedCrossRef

Imig, J. D. (2005). Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. American Journal of Physiology Renal Physiology, 289(3), F496–F503. https://doi.org/10.1152/ajprenal.00350.2004.PubMedCrossRef

10.

Capdevila, J., & Wang, W. (2013). Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension. [Research Support, N.I.H., Extramural Review]. Current Opinion in Nephrology and Hypertension, 22(2), 163–169. https://doi.org/10.1097/MNH.0b013e32835d911e.PubMedPubMedCentralCrossRef

11.

Capdevila, J. H., Wang, W., & Falck, J. R. (2015). Arachidonic acid monooxygenase: genetic and biochemical approaches to physiological/pathophysiological relevance. Prostaglandins & Other Lipid Mediators, 120, 40–49. https://doi.org/10.1016/j.prostaglandins.2015.05.004.CrossRef

12.

Nakagawa, K., Holla, V. R., Wei, Y., Wang, W. H., Gatica, A., Wei, S., et al. (2006). Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel. [research support, N.I.H., extramural research support, non-U.S. Gov’t]. The Journal of Clinical Investigation, 116(6), 1696–1702. https://doi.org/10.1172/JCI27546.PubMedPubMedCentralCrossRef

13.

Jiang, J. G., Chen, C. L., Card, J. W., Yang, S., Chen, J. X., Fu, X. N., Ning, Y. G., Xiao, X., Zeldin, D. C., & Wang, D. W. (2005). Cytochrome P450 2J2 promotes the neoplastic phenotype of carcinoma cells and is up-regulated in human tumors. Cancer Research, 65(11), 4707–4715.PubMedCrossRef

14.

Jiang, J. G., Ning, Y. G., Chen, C., Ma, D., Liu, Z. J., Yang, S., Zhou, J., Xiao, X., Zhang, X. A., Edin, M. L., Card, J. W., Wang, J., Zeldin, D. C., & Wang, D. W. (2007). Cytochrome p450 epoxygenase promotes human cancer metastasis. Cancer Research, 67(14), 6665–6674.PubMedCrossRef

15.

Yang, S., Wei, S., Pozzi, A., & Capdevila, J. H. (2009). The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis. Archives of Biochemistry and Biophysics, 489(1–2), 82–91.PubMedPubMedCentralCrossRef

16.

Pozzi, A., & Capdevila, J. H. (2008). PPARalpha ligands as antitumorigenic and antiangiogenic agents. PPAR Research, 2008, 906542–906548. https://doi.org/10.1155/2008/906542.PubMedPubMedCentralCrossRef

17.

Pozzi, A., Ibanez, M. R., Gatica, A. E., Yang, S., Wei, S., Mei, S., Falck, J. R., & Capdevila, J. H. (2007). Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. The Journal of Biological Chemistry, 282(24), 17685–17695.PubMedCrossRef

18.

Mitra, R., Guo, Z., Milani, M., Mesaros, C., Rodriguez, M., Nguyen, J., Luo, X., Clarke, D., Lamba, J., Schuetz, E., Donner, D. B., Puli, N., Falck, J. R., Capdevila, J., Gupta, K., Blair, I. A., & Potter, D. A. (2011). CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (+/−)-14,15-epoxyeicosatrienoic acid (EET). The Journal of Biological Chemistry, 286(20), 17543–17559. https://doi.org/10.1074/jbc.M110.198515.PubMedPubMedCentralCrossRef

19.

Panigrahy, D., Edin, M. L., Lee, C. R., Huang, S., Bielenberg, D. R., Butterfield, C. E., Barnés, C. M., Mammoto, A., Mammoto, T., Luria, A., Benny, O., Chaponis, D. M., Dudley, A. C., Greene, E. R., Vergilio, J. A., Pietramaggiori, G., Scherer-Pietramaggiori, S. S., Short, S. M., Seth, M., Lih, F. B., Tomer, K. B., Yang, J., Schwendener, R. A., Hammock, B. D., Falck, J. R., Manthati, V. L., Ingber, D. E., Kaipainen, A., D’Amore, P. A., Kieran, M. W., & Zeldin, D. C. (2012). Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. The Journal of Clinical Investigation, 122(1), 178–191. https://doi.org/10.1172/JCI58128.PubMedCrossRef

20.

Seubert, J. M., Zeldin, D. C., Nithipatikom, K., & Gross, G. J. (2007). Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury. Prostaglandins & Other Lipid Mediators, 82(1–4), 50–59. https://doi.org/10.1016/j.prostaglandins.2006.05.017.CrossRef

21.

Campbell, W. B., & Harder, D. R. (1999). Endothelium-derived hyperpolarizing factors and vascular cytochrome P450 metabolites of arachidonic acid in the regulation of tone. Circulation Research, 84(4), 484–488.PubMedCrossRef

22.

Li, P. L., & Campbell, W. B. (1997). Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein. Circulation Research, 80(6), 877–884.PubMedCrossRef

23.

Liu, X., Qian, Z. Y., Xie, F., Fan, W., Nelson, J. W., Xiao, X., Kaul, S., Barnes, A. P., & Alkayed, N. J. (2016). Functional screening for G protein-coupled receptor targets of 14,15-epoxyeicosatrienoic acid. Prostaglandins & Other Lipid Mediators, 132, 31–40. https://doi.org/10.1016/j.prostaglandins.2016.09.002.CrossRef

24.

Pozzi, A., Popescu, V., Yang, S., Mei, S., Shi, M., Puolitaival, S. M., Caprioli, R. M., & Capdevila, J. H. (2010). The anti-tumorigenic properties of peroxisomal proliferator-activated receptor alpha are arachidonic acid epoxygenase-mediated. The Journal of Biological Chemistry, 285(17), 12840–12850.PubMedPubMedCentralCrossRef

25.

Skrypnyk, N., Chen, X., Hu, W., Su, Y., Mont, S., Yang, S., Gangadhariah, M., Wei, S., Falck, J. R., Jat, J. L., Zent, R., Capdevila, J. H., & Pozzi, A. (2014). PPARalpha activation can help prevent and treat non-small cell lung cancer. Cancer Research, 74(2), 621–631. https://doi.org/10.1158/0008-5472.CAN-13-1928.PubMedCrossRef

26.

Guo, Z., Sevrioukova, I. F., Denisov, I. G., Zhang, X., Chiu, T.-L., Thomas, D. G., Hanse, E. A., Cuellar, R. A. D., Grinkova, Y. V., Langenfeld, V. W., Swedien, D. S., Stamschror, J. D., Alvarez, J., Luna, F., Galván, A., Bae, Y. K., Wulfkuhle, J. D., Gallagher, R. I., Petricoin 3rd, E. F., Norris, B., Flory, C. M., Schumacher, R. J., O'Sullivan, M. G., Cao, Q., Chu, H., Lipscomb, J. D., Atkins, W. M., Gupta, K., Kelekar, A., Blair, I. A., Capdevila, J. H., Falck, J. R., Sligar, S. G., Poulos, T. L., Georg, G. I., Ambrose, E., & Potter, D. A. (2017). Heme binding biguanides target cytochrome P450-dependent cancer cell mitochondria. Cell Chemical Biology, 24(10), 1259–1275. https://doi.org/10.1016/j.chembiol.2017.08.009.PubMedCrossRef

27.

Thuy Phuong, N. T., Kim, J. W., Kim, J. A., Jeon, J. S., Lee, J. Y., Xu, W. J., et al. (2017). Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the development of tamoxifen-resistant breast cancer. Oncotarget, 8(41), 71054–71069. https://doi.org/10.18632/oncotarget.20329.PubMedPubMedCentralCrossRef

28.

Cheranov, S. Y., Karpurapu, M., Wang, D., Zhang, B., Venema, R. C., & Rao, G. N. (2008). An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis. Blood, 111(12), 5581–5591.PubMedPubMedCentralCrossRef

29.

Webler, A. C., Michaelis, U. R., Popp, R., Barbosa-Sicard, E., Murugan, A., Falck, J. R., Fisslthaler, B., & Fleming, I. (2008). Epoxyeicosatrienoic acids are part of the VEGF-activated signaling cascade leading to angiogenesis. American journal of physiology. Cell Physiology, 295(5), C1292–C1301.PubMedPubMedCentralCrossRef

30.

Rodriguez-Antona, C., & Ingelman-Sundberg, M. (2006). Cytochrome P450 pharmacogenetics and cancer. Oncogene, 25(11), 1679–1691. https://doi.org/10.1038/sj.onc.1209377.PubMedCrossRef

31.

Murray, G. I., Patimalla, S., Stewart, K. N., Miller, I. D., & Heys, S. D. (2010). Profiling the expression of cytochrome P450 in breast cancer. Histopathology, 57(2), 202–211.PubMedCrossRef

32.

Rifkind, A. B., Lee, C., Chang, T. K., & Waxman, D. J. (1995). Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Archives of Biochemistry and Biophysics, 320(2), 380–389.PubMedCrossRef

33.

Mesaros, C., Lee, S. H., & Blair, I. A. (2010). Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards. [Research Support, N.I.H., Extramural]. Rapid Communications in Mass Spectrometry : RCM, 24(22), 3237–3247. https://doi.org/10.1002/rcm.4760.PubMedCrossRef

34.

Zeldin, D. C., DuBois, R. N., Falck, J. R., & Capdevila, J. H. (1995). Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform. Archives of Biochemistry and Biophysics, 322(1), 76–86.PubMedCrossRef

35.

Zeldin, D. C., Moomaw, C. R., Jesse, N., Tomer, K. B., Beetham, J., Hammock, B. D., & Wu, S. (1996). Biochemical characterization of the human liver cytochrome P450 arachidonic acid epoxygenase pathway. [Comparative Study Research Support, U.S. Gov’t, P.H.S.]. Archives of Biochemistry and Biophysics, 330(1), 87–96. https://doi.org/10.1006/abbi.1996.0229.PubMedCrossRef

36.

Zeldin, D. C., Foley, J., Ma, J., Boyle, J. E., Pascual, J. M., Moomaw, C. R., et al. (1996). CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. Molecular Pharmacology, 50(5), 1111–1117.PubMed

37.

Carver, K. A., Lourim, D., Tryba, A. K., & Harder, D. R. (2014). Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature. American journal of physiology. Cell physiology, 307(11), C989–C998. https://doi.org/10.1152/ajpcell.00401.2013.PubMedPubMedCentralCrossRef

38.

Askari, A., Thomson, S. J., Edin, M. L., Zeldin, D. C., & Bishop-Bailey, D. (2013). Roles of the epoxygenase CYP2J2 in the endothelium. [Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t Review]. Prostaglandins & Other Lipid Mediators, 107, 56–63. https://doi.org/10.1016/j.prostaglandins.2013.02.003.CrossRef

39.

Michaelis, U. R., Fisslthaler, B., Barbosa-Sicard, E., Falck, J. R., Fleming, I., & Busse, R. (2005). Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis. Journal of Cell Science, 118(Pt 23), 5489–5498.PubMedCrossRef

40.

Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D. R., Fleming, I., et al. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature, 401(6752), 493–497. https://doi.org/10.1038/46816.PubMedCrossRef

41.

Siest, G., Jeannesson, E., Marteau, J. B., Samara, A., Marie, B., Pfister, M., & Visvikis-Siest, S. (2008). Transcription factor and drug-metabolizing enzyme gene expression in lymphocytes from healthy human subjects. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 36(1), 182–189. https://doi.org/10.1124/dmd.107.017228.CrossRef

42.

Lee, S. H., Williams, M. V., DuBois, R. N., & Blair, I. A. (2003). Targeted lipidomics using electron capture atmospheric pressure chemical ionization mass spectrometry. Rapid Communications in Mass Spectrometry : RCM, 17(19), 2168–2176.PubMedCrossRef

43.

Mesaros, C., Lee, S. H., & Blair, I. A. (2009). Targeted quantitative analysis of eicosanoid lipids in biological samples using liquid chromatography-tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 877(26), 2736–2745.PubMedPubMedCentralCrossRef

44.

Chacos, N., Capdevila, J., Falck, J. R., Manna, S., Martin-Wixtrom, C., Gill, S. S., Hammock, B. D., & Estabrook, R. W. (1983). The reaction of arachidonic acid epoxides (epoxyeicosatrienoic acids) with a cytosolic epoxide hydrolase. [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]. Archives of Biochemistry and Biophysics, 223(2), 639–648.PubMedCrossRef

45.

Zeldin, D. C., Wei, S., Falck, J. R., Hammock, B. D., Snapper, J. R., & Capdevila, J. H. (1995). Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. Archives of Biochemistry and Biophysics, 316(1), 443–451.PubMedCrossRef

46.

Zhang, G., Kodani, S., & Hammock, B. D. (2014). Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer. Progress in Lipid Research, 53, 108–123. https://doi.org/10.1016/j.plipres.2013.11.003.PubMedCrossRef

47.

Zhang, G., Panigrahy, D., Mahakian, L. M., Yang, J., Liu, J. Y., Stephen Lee, K. S., Wettersten, H. I., Ulu, A., Hu, X., Tam, S., Hwang, S. H., Ingham, E. S., Kieran, M. W., Weiss, R. H., Ferrara, K. W., & Hammock, B. D. (2013). Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]. Proceedings of the National Academy of Sciences of the United States of America, 110(16), 6530–6535. https://doi.org/10.1073/pnas.1304321110.PubMedPubMedCentralCrossRef

48.

Osanai, M., Sawada, N., & Lee, G. H. (2010). Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1. Oncogene, 29(8), 1135–1144. https://doi.org/10.1038/onc.2009.414.PubMedCrossRef

49.

Michaelis, U. R., Fisslthaler, B., Medhora, M., Harder, D., Fleming, I., & Busse, R. (2003). Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR). FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 17(6), 770–772. https://doi.org/10.1096/fj.02-0640fje.CrossRef

50.

Larsen, B. T., Gutterman, D. D., & Hatoum, O. A. (2006). Emerging role of epoxyeicosatrienoic acids in coronary vascular function. European Journal of Clinical Investigation, 36(5), 293–300. https://doi.org/10.1111/j.1365-2362.2006.01634.x.PubMedCrossRef

51.

Wang, D., & Dubois, R. N. (2012). Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer. The Journal of Clinical Investigation, 122(1), 19–22. https://doi.org/10.1172/JCI61453.PubMedCrossRef

52.

Seubert, J., Yang, B., Bradbury, J. A., Graves, J., Degraff, L. M., Gabel, S., et al. (2004). Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circulation Research, 95(5), 506–514. https://doi.org/10.1161/01.RES.0000139436.89654.c8.PubMedCrossRef

53.

Seubert, J. M., Sinal, C. J., Graves, J., DeGraff, L. M., Bradbury, J. A., Lee, C. R., et al. (2006). Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function. Circulation Research, 99(4), 442–450. https://doi.org/10.1161/01.RES.0000237390.92932.37.PubMedPubMedCentralCrossRef

54.

Borzelleca, J. F. (2000). Paracelsus: herald of modern toxicology. Toxicological Sciences : an Official Journal of the Society of Toxicology, 53(1), 2–4.CrossRef

55.

Inceoglu, B., Jinks, S. L., Schmelzer, K. R., Waite, T., Kim, I. H., & Hammock, B. D. (2006). Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sciences, 79(24), 2311–2319. https://doi.org/10.1016/j.lfs.2006.07.031.PubMedPubMedCentralCrossRef

56.

Rose, T. E., Morisseau, C., Liu, J. Y., Inceoglu, B., Jones, P. D., Sanborn, J. R., & Hammock, B. D. (2010). 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain. Journal of Medicinal Chemistry, 53(19), 7067–7075. https://doi.org/10.1021/jm100691c.PubMedPubMedCentralCrossRef

57.

Chen, C., Wei, X., Rao, X., Wu, J., Yang, S., Chen, F., Ma, D., Zhou, J., Dackor, R. T., Zeldin, D. C., & Wang, D. W. (2011). Cytochrome P450 2J2 is highly expressed in hematologic malignant diseases and promotes tumor cell growth. The Journal of Pharmacology and Experimental Therapeutics, 336(2), 344–355. https://doi.org/10.1124/jpet.110.174805.PubMedPubMedCentralCrossRef

58.

Enayetallah, A. E., French, R. A., & Grant, D. F. (2006). Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms. Journal of Molecular Histology, 37(3–4), 133–141.PubMedCrossRef

59.

Pozzi, A., Macias-Perez, I., Abair, T., Wei, S., Su, Y., Zent, R., Falck, J. R., & Capdevila, J. H. (2005). Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids. The Journal of Biological Chemistry, 280(29), 27138–27146.PubMedCrossRef

60.

Gilroy, D. W., Edin, M. L., De Maeyer, R. P., Bystrom, J., Newson, J., Lih, F. B., et al. (2016). CYP450-derived oxylipins mediate inflammatory resolution. Proceedings of the National Academy of Sciences of the United States of America, 113(23), E3240–E3249. https://doi.org/10.1073/pnas.1521453113.PubMedPubMedCentralCrossRef

61.

Schmelzle, M., Dizdar, L., Matthaei, H., Baldus, S. E., Wolters, J., Lindenlauf, N., Bruns, I., Cadeddu, R. P., Kröpil, F., Topp, S. A., Schulte am Esch II, J., Eisenberger, C. F., Knoefel, W. T., & Stoecklein, N. H. (2011). Esophageal cancer proliferation is mediated by cytochrome P450 2C9 (CYP2C9). Prostaglandins & Other Lipid Mediators, 94(1–2), 25–33. https://doi.org/10.1016/j.prostaglandins.2010.12.001.CrossRef

62.

Oguro, A., Sakamoto, K., Funae, Y., & Imaoka, S. (2011). Overexpression of CYP3A4, but not CYP2D6, promotes hypoxic response and cell growth of Hep3B cells. Drug metabolism and Pharmacokinetics, 26, 407–415.PubMedCrossRef

63.

Shao, J., Li, Q., Wang, H., Liu, F., Jiang, J., Zhu, X., Chen, Z., & Zou, P. (2011). P-450-dependent epoxygenase pathway of arachidonic acid is involved in myeloma-induced angiogenesis of endothelial cells. Journal of Huazhong University of Science and Technology. Medical Sciences, 31(5), 596–601. https://doi.org/10.1007/s11596-011-0567-0.CrossRef

64.

Shao, J., Wang, H., Yuan, G., Chen, Z., & Li, Q. (2016). Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells. PeerJ, 4, e1925. https://doi.org/10.7717/peerj.1925.PubMedPubMedCentralCrossRef

65.

Wei, X., Zhang, D., Dou, X., Niu, N., Huang, W., Bai, J., et al. (2014). Elevated 14,15- epoxyeicosatrienoic acid by increasing of cytochrome P450 2C8, 2C9 and 2J2 and decreasing of soluble epoxide hydrolase associated with aggressiveness of human breast cancer. [Research Support, Non-U.S. Gov’t]. BMC Cancer, 14, 841. https://doi.org/10.1186/1471-2407-14-841.PubMedPubMedCentralCrossRef

66.

Floriano-Sanchez, E., Rodriguez, N. C., Bandala, C., Coballase-Urrutia, E., & Lopez-Cruz, J. (2014). CYP3A4 expression in breast cancer and its association with risk factors in Mexican women. [Research Support, Non-U.S. Gov’t]. Asian Pacific Journal of Cancer Prevention : APJCP, 15(8), 3805–3809.PubMedCrossRef

67.

Bajpai, P., Srinivasan, S., Ghosh, J., Nagy, L. D., Wei, S., Guengerich, F. P., & Avadhani, N. G. (2014). Targeting of splice variants of human cytochrome P450 2C8 (CYP2C8) to mitochondria and their role in arachidonic acid metabolism and respiratory dysfunction. The Journal of Biological Chemistry, 289(43), 29614–29630. https://doi.org/10.1074/jbc.M114.583062.PubMedPubMedCentralCrossRef

68.

Zou, A. P., Ma, Y. H., Sui, Z. H., Ortiz de Montellano, P. R., Clark, J. E., Masters, B. S., et al. (1994). Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats. The Journal of Pharmacology and Experimental Therapeutics, 268(1), 474–481.PubMed

69.

Wang, M. H., Brand-Schieber, E., Zand, B. A., Nguyen, X., Falck, J. R., Balu, N., et al. (1998). Cytochrome P450-derived arachidonic acid metabolism in the rat kidney: characterization of selective inhibitors. The Journal of Pharmacology and Experimental Therapeutics, 284(3), 966–973.PubMed

70.

Zou, A. P., Imig, J. D., Kaldunski, M., Ortiz de Montellano, P. R., Sui, Z., & Roman, R. J. (1994). Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow. The American Journal of Physiology, 266(2 Pt 2), F275–F282. https://doi.org/10.1152/ajprenal.1994.266.2.F275.PubMedCrossRef

71.

Brand-Schieber, E., Falck, J. F., & Schwartzman, M. (2000). Selective inhibition of arachidonic acid epoxidation in vivo. Journal of Physiology and Pharmacology, 51(4 Pt 1), 655–672.PubMed

72.

Lin, H.-l., Zhang, H., Walker, V. J., D’Agostino, J., & Hollenberg, P. F. (2017). Heme modification contributes to the mechanism-based inactivation of human cytochrome P450 2J2 by two terminal acetylenic compounds. Drug Metabolism and Disposition, 45(9), 990.PubMedPubMedCentralCrossRef

73.

Arrowsmith, C. H., Audia, J. E., Austin, C., Baell, J., Bennett, J., Blagg, J., Bountra, C., Brennan, P. E., Brown, P. J., Bunnage, M. E., Buser-Doepner, C., Campbell, R. M., Carter, A. J., Cohen, P., Copeland, R. A., Cravatt, B., Dahlin, J. L., Dhanak, D., Edwards, A. M., Frederiksen, M., Frye, S. V., Gray, N., Grimshaw, C. E., Hepworth, D., Howe, T., Huber, K. V. M., Jin, J., Knapp, S., Kotz, J. D., Kruger, R. G., Lowe, D., Mader, M. M., Marsden, B., Mueller-Fahrnow, A., Müller, S., O'Hagan, R. C., Overington, J. P., Owen, D. R., Rosenberg, S. H., Ross, R., Roth, B., Schapira, M., Schreiber, S. L., Shoichet, B., Sundström, M., Superti-Furga, G., Taunton, J., Toledo-Sherman, L., Walpole, C., Walters, M. A., Willson, T. M., Workman, P., Young, R. N., & Zuercher, W. J. (2015). The promise and peril of chemical probes. Nature Chemical Biology, 11(8), 536–541. https://doi.org/10.1038/nchembio.1867.PubMedPubMedCentralCrossRef

74.

Sisignano, M., Angioni, C., Park, C. K., Meyer Dos Santos, S., Jordan, H., Kuzikov, M., Liu, D., Zinn, S., Hohman, S. W., Schreiber, Y., Zimmer, B., Schmidt, M., Lu, R., Suo, J., Zhang, D. D., Schäfer, S. M. G., Hofmann, M., Yekkirala, A. S., de Bruin, N., Parnham, M. J., Woolf, C. J., Ji, R. R., Scholich, K., & Geisslinger, G. (2016). Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain. Proceedings of the National Academy of Sciences of the United States of America, 113(44), 12544–12549. https://doi.org/10.1073/pnas.1613246113.PubMedPubMedCentralCrossRef

75.

Chen, C., Li, G., Liao, W., Wu, J., Liu, L., Ma, D., Zhou, J., Elbekai, R. H., Edin, M. L., Zeldin, D. C., & Wang, D. W. (2009). Selective inhibitors of CYP2J2 related to terfenadine exhibit strong activity against human cancers in vitro and in vivo. The Journal of Pharmacology and Experimental Therapeutics, 329(3), 908–918.PubMedPubMedCentralCrossRef

76.

Nithipatikom, K., Brody, D. M., Tang, A. T., Manthati, V. L., Falck, J. R., Williams, C. L., & Campbell, W. B. (2010). Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists. Cancer Science, 101(12), 2629–2636. https://doi.org/10.1111/j.1349-7006.2010.01713.x.PubMedPubMedCentralCrossRef

77.

Vriens, J., Owsianik, G., Fisslthaler, B., Suzuki, M., Janssens, A., Voets, T., et al. (2005). Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. [Research Support, Non-U.S. Gov’t]. Circulation Research, 97(9), 908–915. https://doi.org/10.1161/01.RES.0000187474.47805.30.PubMedCrossRef

78.

Chong, C. R., Xu, J., Lu, J., Bhat, S., Sullivan Jr., D. J., & Liu, J. O. (2007). Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chemical Biology, 2(4), 263–270. https://doi.org/10.1021/cb600362d.PubMedCrossRef

79.

Ernest 2nd, C. S., Hall, S. D., & Jones, D. R. (2005). Mechanism-based inactivation of CYP3A by HIV protease inhibitors. The Journal of Pharmacology and Experimental Therapeutics, 312(2), 583–591.PubMedCrossRef

80.

Gaedicke, S., Firat-Geier, E., Constantiniu, O., Lucchiari-Hartz, M., Freudenberg, M., Galanos, C., et al. (2002). Antitumor effect of the human immunodeficiency virus protease inhibitor ritonavir: induction of tumor-cell apoptosis associated with perturbation of proteasomal proteolysis. Cancer Research, 62(23), 6901–6908.PubMed

81.

Katragadda, D., Batchu, S. N., Cho, W. J., Chaudhary, K. R., Falck, J. R., & Seubert, J. M. (2009). Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. [Research Support, Non-U.S. Gov’t]. Journal of Molecular and Cellular Cardiology, 46(6), 867–875. https://doi.org/10.1016/j.yjmcc.2009.02.028.PubMedCrossRef

82.

Liu, L., Chen, C., Gong, W., Li, Y., Edin, M. L., Zeldin, D. C., & Wang, D. W. (2011). Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide. [Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t]. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 451–463. https://doi.org/10.1124/jpet.111.180505.PubMedPubMedCentralCrossRef

83.

Ghersi-Egea, J. F., Perrin, R., Leininger-Muller, B., Grassiot, M. C., Jeandel, C., Floquet, J., Cuny, G., Siest, G., & Minn, A. (1993). Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain. Biochemical Pharmacology, 45(3), 647–658.PubMedCrossRef

84.

Su, P., Rennert, H., Shayiq, R. M., Yamamoto, R., Zheng, Y. M., Addya, S., et al. (1990). A cDNA encoding a rat mitochondrial cytochrome P450 catalyzing both the 26-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3: gonadotropic regulation of the cognate mRNA in ovaries. DNA and Cell Biology, 9(9), 657–667. https://doi.org/10.1089/dna.1990.9.657.PubMedCrossRef

85.

de Brito, O. M., & Scorrano, L. (2010). An intimate liaison: spatial organization of the endoplasmic reticulum-mitochondria relationship. The EMBO Journal, 29(16), 2715–2723. https://doi.org/10.1038/emboj.2010.177.PubMedPubMedCentralCrossRef

86.

Sepuri, N. B., Yadav, S., Anandatheerthavarada, H. K., & Avadhani, N. G. (2007). Mitochondrial targeting of intact CYP2B1 and CYP2E1 and N-terminal truncated CYP1A1 proteins in Saccharomyces cerevisiae--role of protein kinase A in the mitochondrial targeting of CYP2E1. The FEBS Journal, 274(17), 4615–4630. https://doi.org/10.1111/j.1742-4658.2007.05990.x.PubMedCrossRef

87.

Addya, S., Anandatheerthavarada, H. K., Biswas, G., Bhagwat, S. V., Mullick, J., & Avadhani, N. G. (1997). Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2. The Journal of Cell Biology, 139(3), 589–599.PubMedPubMedCentralCrossRef

88.

Robin, M. A., Anandatheerthavarada, H. K., Fang, J. K., Cudic, M., Otvos, L., & Avadhani, N. G. (2001). Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N terminus and requires mitochondrial specific electron transfer proteins for activity. The Journal of Biological Chemistry, 276(27), 24680–24689. https://doi.org/10.1074/jbc.M100363200.PubMedCrossRef

89.

Bansal, S., Leu, A. N., Gonzalez, F. J., Guengerich, F. P., Chowdhury, A. R., Anandatheerthavarada, H. K., & Avadhani, N. G. (2014). Mitochondrial targeting of cytochrome P450 (CYP) 1B1 and its role in polycyclic aromatic hydrocarbon-induced mitochondrial dysfunction. The Journal of Biological Chemistry, 289(14), 9936–9951. https://doi.org/10.1074/jbc.M113.525659.PubMedPubMedCentralCrossRef

90.

Srirangam, A., Mitra, R., Wang, M., Gorski, J. C., Badve, S., Baldridge, L., et al. (2006). Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 12(6), 1883–1896.CrossRef

91.

Srirangam, A., Milani, M., Mitra, R., Guo, Z., Rodriguez, M., Kathuria, H., Fukuda, S., Rizzardi, A., Schmechel, S., Skalnik, D. G., Pelus, L. M., & Potter, D. A. (2011). The human immunodeficiency virus protease inhibitor ritonavir inhibits lung cancer cells, in part, by inhibition of survivin. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Journal of Thoracic Cncology : Official Publication of the International Association for the Study of Lung Cancer, 6(4), 661–670. https://doi.org/10.1097/JTO.0b013e31820c9e3c.CrossRef

92.

Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., Reya, T., Liu, J. O., Epstein, E. H., Stevens, D. A., & Beachy, P. A. (2010). Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 17(4), 388–399. https://doi.org/10.1016/j.ccr.2010.02.027.PubMedPubMedCentralCrossRef

93.

Wang, X., Wei, S., Zhao, Y., Shi, C., Liu, P., Zhang, C., Lei, Y., Zhang, B., Bai, B., Huang, Y., & Zhang, H. (2017). Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death. Cancer Letters, 385, 128–136. https://doi.org/10.1016/j.canlet.2016.10.034.PubMedCrossRef

94.

Phuong, N. T. T., Kim, J. W., Kim, J.-A., Jeon, J. S., Lee, J.-Y., Xu, W. J., et al. (2017). Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the development of tamoxifen-resistant breast cancer. Oncotarget, 8(41), doi: 10.18632/oncotarget.20329.

95.

Forgue-Lafitte, M. E., Coudray, A. M., Fagot, D., & Mester, J. (1992). Effects of ketoconazole on the proliferation and cell cycle of human cancer cell lines. Cancer Research, 52(24), 6827–6831.PubMed

96.

Choi, Y. H., & Lee, M. G. (2012). Pharmacokinetic and pharmacodynamic interaction between nifedipine and metformin in rats: competitive inhibition for metabolism of nifedipine and metformin by each other via CYP isozymes. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 42(5), 483–495. https://doi.org/10.3109/00498254.2011.633177.PubMedCrossRef

97.

Choi, Y. H., Lee, U., Lee, B. K., & Lee, M. G. (2010). Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2. [Research Support, Non-U.S. Gov’t]. British Journal of Pharmacology, 161(4), 815–829. https://doi.org/10.1111/j.1476-5381.2010.00913.x.PubMedPubMedCentralCrossRef

98.

Dowling, R. J., Zakikhani, M., Fantus, I. G., Pollak, M., & Sonenberg, N. (2007). Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. [Research Support, Non-U.S. Gov’t]. Cancer Research, 67(22), 10804–10812. https://doi.org/10.1158/0008-5472.CAN-07-2310.PubMedCrossRef

99.

Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M. (2006). Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. [Research Support, Non-U.S. Gov’t]. Cancer Research, 66(21), 10269–10273. https://doi.org/10.1158/0008-5472.CAN-06-1500.PubMedCrossRef

100.

Zakikhani, M., Blouin, M. J., Piura, E., & Pollak, M. N. (2010). Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. [Research Support, Non-U.S. Gov’t]. Breast Cancer Research and Treatment, 123(1), 271–279. https://doi.org/10.1007/s10549-010-0763-9.PubMedCrossRef

101.

Deng, X. S., Wang, S., Deng, A., Liu, B., Edgerton, S. M., Lind, S. E., Wahdan-Alaswad, R., & Thor, A. D. (2012). Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers. Cell Cycle, 11(2), 367–376. https://doi.org/10.4161/cc.11.2.18813.PubMedCrossRef

102.

Chandel, N. S., Avizonis, D., Reczek, C. R., Weinberg, S. E., Menz, S., Neuhaus, R., Christian, S., Haegebarth, A., Algire, C., & Pollak, M. (2016). Are metformin doses used in murine cancer models clinically relevant? Cell Metabolism, 23(4), 569–570. https://doi.org/10.1016/j.cmet.2016.03.010.PubMedCrossRef

103.

Kim, S. W., Jun, S. S., Min, C. H., Kim, Y. W., Kang, M., S, Oh, B. K., et al. (2011). Biguanide derivative, a preparation method thereof and a pharmaceutical composition containing the biguanide derivative as an active ingredient. . In U. S. P. a. T. Office (Ed.), Patent application WO 2011083998 (Vol. A1, pp. 1–14). Korea: Hanall Biopharma Co., Ltd.

104.

Eagling, V. A., Back, D. J., & Barry, M. G. (1997). Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. British Journal of Clinical Pharmacology, 44(2), 190–194.PubMedPubMedCentralCrossRef

105.

Akiyoshi, T., Saito, T., Murase, S., Miyazaki, M., Murayama, N., Yamazaki, H., Guengerich, F. P., Nakamura, K., Yamamoto, K., & Ohtani, H. (2011). Comparison of the inhibitory profiles of itraconazole and cimetidine in cytochrome P450 3A4 genetic variants. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 39(4), 724–728. https://doi.org/10.1124/dmd.110.036780.CrossRef

106.

Ikezoe, T., Saito, T., Bandobashi, K., Yang, Y., Koeffler, H. P., & Taguchi, H. (2004). HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2. Molecular Cancer Therapeutics, 3(4), 473–479.PubMed

107.

Scharping, N. E., Menk, A. V., Whetstone, R. D., Zeng, X., & Delgoffe, G. M. (2017). Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia. Cancer Immunology Research, 5(1), 9–16. https://doi.org/10.1158/2326-6066.CIR-16-0103.PubMedCrossRef

108.

Allison, S. E., Chen, Y., Petrovic, N., Zhang, J., Bourget, K., Mackenzie, P. I., & Murray, M. (2017). Activation of ALDH1A1 in MDA-MB-468 breast cancer cells that over-express CYP2J2 protects against paclitaxel-dependent cell death mediated by reactive oxygen species. Biochemical Pharmacology, 143, 79–89. https://doi.org/10.1016/j.bcp.2017.07.020.PubMedCrossRef

109.

Cristofanilli, M., Turner, N. C., Bondarenko, I., Ro, J., Im, S. A., Masuda, N., Colleoni, M., DeMichele, A., Loi, S., Verma, S., Iwata, H., Harbeck, N., Zhang, K., Theall, K. P., Jiang, Y., Bartlett, C. H., Koehler, M., & Slamon, D. (2016). Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. The Lancet Oncology, 17(4), 425–439. https://doi.org/10.1016/S1470-2045(15)00613-0.PubMedCrossRef

110.

Sledge Jr., G. W., Toi, M., Neven, P., Sohn, J., Inoue, K., Pivot, X., Burdaeva, O., Okera, M., Masuda, N., Kaufman, P. A., Koh, H., Grischke, E. M., Frenzel, M., Lin, Y., Barriga, S., Smith, I. C., Bourayou, N., & Llombart-Cussac, A. (2017). MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 35(25), 2875–2884. https://doi.org/10.1200/JCO.2017.73.7585.CrossRef

111.

Zhang, Y., El-Sikhry, H., Chaudhary, K. R., Batchu, S. N., Shayeganpour, A., Jukar, T. O., et al. (2009). Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity. [Research Support, Non-U.S. Gov’t]. American Journal of Physiology. Heart and Circulatory Physiology, 297(1), H37–H46. https://doi.org/10.1152/ajpheart.00983.2008.PubMedPubMedCentralCrossRef

112.

Kaur, P., Chamberlin, A. R., Poulos, T. L., & Sevrioukova, I. F. (2016). Structure-based inhibitor design for evaluation of a CYP3A4 pharmacophore model. Journal of Medicinal Chemistry, 59(9), 4210–4220. https://doi.org/10.1021/acs.jmedchem.5b01146.PubMedCrossRef

Title: Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them
Authors: Zhijun Guo
Veronica Johnson
Jaime Barrera
Mariel Porras
Diego Hinojosa
Irwin Hernández
Patrick McGarrah
David A. Potter
Publication date: 01-09-2018
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 2-3/2018
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-018-9749-6

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

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