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Involvement of cytochrome P450 enzymes in inflammation and cancer: a review

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Abstract

Cytochrome P450 (CYP) enzymes are responsible for the biotransformation of drugs, xenobiotics, and endogenous substances. This enzymatic activity can be modulated by intrinsic and extrinsic factors, modifying the organism’s response to medications. Among the factors that are responsible for enzyme inhibition or induction is the release of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ), from macrophages, lymphocytes, and neutrophils. These cells are also present in the tumor microenvironment, participating in the development of cancer, a disease that is characterized by cellular mutations that favor cell survival and proliferation. Mutations also occur in CYP enzymes, resulting in enzymatic polymorphisms and modulation of their activity. Therefore, the inhibition or induction of CYP enzymes by proinflammatory cytokines in the tumor microenvironment can promote carcinogenesis and affect chemotherapy, resulting in adverse effects, toxicity, or therapeutic failure. This review discusses the relevance of CYPs in hepatocarcinoma, breast cancer, lung cancer, and chemotherapy by reviewing in vitro, in vivo, and clinical studies. We also discuss the importance of elucidating the relationships between inflammation, CYPs, and cancer to predict drug interactions and therapeutic efficacy.

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Abbreviations

4-OHCP:

4-Hydroxy-cyclophosphamide

20-HETE:

Hydroxyeicosatetranoic acid

AC:

Doxorubicin and cyclophosphamide

AhR:

Aryl hydrocarbon receptor

ARNT:

Aryl hydrocarbon receptor nuclear translocator

CAR:

Constitutive androstane receptor

CYP450:

Cytochrome P450

DNA:

Deoxyribonucleic acid

E2:

Estradiol

EET:

4-Epoxyeicosatrienoic

ERs:

Estrogen receptors

ERCC1:

Repair cross-complementary 1

HCC:

Liver hepatocellular carcinoma

HCV:

Hepatitis C virus

HBV:

Hepatitis B virus

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

IL-1:

Interleukin-1

IL-6:

Interleukin-6

IFN-γ:

Interferon-γ

Ki :

Inhibitory constants

LPS:

Lipopolysaccharide

LTA:

Lipotechoic acid

mRNA:

Messenger ribonucleic acid

Mrp2:

Multidrug resistance-associated protein 2

PXR:

Pregnane X receptor

Sultn:

Amine N-sulfotransferase

TGF-β:

Transforming growth factor β

TNF-α:

Tumor necrosis factor α

Ugt1a1:

UDP glucuronosyltransferase family 1 member A1

Vmax :

Maximal metabolic velocity

XREs:

Xenobiotic response elements

References

  1. Stavropoulou E, Pircalabioru GG, Bezirtzoglou E (2018) The role of cytochromes P450 in infection. Front Immunol 9:1–7. https://doi.org/10.3389/fimmu.2018.00089

    Article  CAS  Google Scholar 

  2. Christmas P (2015) Role of cytochrome P450s in inflammation. In: advances in pharmacology. Elsevier, London

    Book  Google Scholar 

  3. He X, Feng S (2015) Role of metabolic enzymes P450 (CYP) on activating procarcinogen and their polymorphisms on the risk of cancers. Curr Drug Metab 16:850–863. https://doi.org/10.2174/138920021610151210164501

    Article  CAS  PubMed  Google Scholar 

  4. Oyama T (2007) Cytochrome P450 expression (CYP) in non-small cell lung cancer. Front Biosci 12:2299. https://doi.org/10.2741/2232

    Article  CAS  PubMed  Google Scholar 

  5. Korobkova EA (2015) Effect of natural polyphenols on CYP metabolism: implications for diseases. Chem Res Toxicol 28:1359–1390. https://doi.org/10.1021/acs.chemrestox.5b00121

    Article  CAS  PubMed  Google Scholar 

  6. Guengerich F (2014) Analysis and characterization of enzymes and nucleic acids relevant to toxicology. In: Hayes’ principles and methods of toxicology. CRC Press, Newyork

    Book  Google Scholar 

  7. Nebert DW, Wikvall K, Miller WL (2013) Human cytochromes P450 in health and disease. Philos Trans R Soc Lond B Biol Sci 368:20120431. https://doi.org/10.1098/rstb.2012.0431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fan Z, Wang Z, Chen W et al (2016) Association between the CYP11 family and six cancer types. Oncol Lett 12:35–40. https://doi.org/10.3892/ol.2016.4567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Furge LL, Guengerich FP (2006) Cytochrome P450 enzymes in drug metabolism and chemical toxicology: an introduction. Biochem Mol Biol Educ 34:66–74

    Article  CAS  Google Scholar 

  10. Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 239:2379–2385

    Article  CAS  Google Scholar 

  11. Moriya N, Kataoka H, Fujino H et al (2012) Effect of lipopolysaccharide on the xenobiotic-induced expression and activity of hepatic cytochrome P450 in mice. Biol Pharm Bull 35:473–480. https://doi.org/10.1248/bpb.35.473

    Article  CAS  PubMed  Google Scholar 

  12. Van der Weide J, Steijns LS (1999) Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 36(Pt 6):722–729

    Article  Google Scholar 

  13. Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138:103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007

    Article  CAS  Google Scholar 

  14. Robottom-Ferreira AB, Aquino SR, Queiroga R et al (2003) Expression of CYP2A3 mRNA and its regulation by 3-methylcholanthrene, pyrazole, and ??-ionone in rat tissues. Br J Med Biol Res 36:839–844. https://doi.org/10.1590/S0100-879X2003000700003

    Article  CAS  Google Scholar 

  15. Gaudet P, Livstone MS, Lewis SE, Thomas PD (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief Bioinform 12:449–462. https://doi.org/10.1093/bib/bbr042

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jeong S, Nguyen PD, Desta Z (2009) Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother 53:541–551. https://doi.org/10.1128/AAC.01123-08

    Article  CAS  PubMed  Google Scholar 

  17. Gopalakrishnan R, Gupta A, Carlton PS et al (2002) Functional role of cytochrome p-450 2a3 in N-nitrosomethylbenzylamine metabolism in rat esophagus. J Toxicol Environ Health A 65:1077–1091. https://doi.org/10.1080/152873902760125237

    Article  CAS  PubMed  Google Scholar 

  18. Yano JK, Hsu M-H, Griffin KJ et al (2005) Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol 12:822–823. https://doi.org/10.1038/nsmb971

    Article  CAS  PubMed  Google Scholar 

  19. Tanner J-A, Tyndale R (2017) Variation in CYP2A6 activity and personalized medicine. J Pers Med 7:18. https://doi.org/10.3390/jpm7040018

    Article  PubMed Central  Google Scholar 

  20. Kilanowicz A, Czekaj P, Sapota A et al (2015) Developmental toxicity of hexachloronaphthalene in Wistar rats. A role of CYP1A1 expression. Reprod Toxicol 58:93–103. https://doi.org/10.1016/j.reprotox.2015.09.005

    Article  CAS  PubMed  Google Scholar 

  21. Lee AJ, Conney AH, Zhu BT (2003) Human cytochrome P450 3A7 has a distinct high catalytic activity for the 16??-hydroxylation of estrone but not 17??-estradiol. Cancer Res 63:6532–6536

    CAS  PubMed  Google Scholar 

  22. Laine JE, Auriola S, Pasanen M, Juvonen RO (2009) Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica 39:11–21. https://doi.org/10.1080/00498250802512830

    Article  CAS  PubMed  Google Scholar 

  23. Kawajiri K, Nakachi K, Imai K et al (1990) Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett 263:131–133. https://doi.org/10.1016/0014-5793(90)80721-T

    Article  CAS  PubMed  Google Scholar 

  24. Gupta RP, He YA, Patrick KS et al (2005) CYP3A4 is a vitamin D-24- and 25-hydroxylase: Analysis of structure function by site-directed mutagenesis. J Clin Endocrinol Metab 90:1210–1219. https://doi.org/10.1210/jc.2004-0966

    Article  CAS  PubMed  Google Scholar 

  25. Anwar-Mohamed A, Elbekai RH, El-Kadi AOS (2009) Regulation of CYP1A1 by heavy metals and consequences for drug metabolism. Expert Opin Drug Metab Toxicol 5:501–521. https://doi.org/10.1517/17425250902918302

    Article  CAS  PubMed  Google Scholar 

  26. Sciarra A, Pintea B, Nahm JH et al (2017) CYP1A2 is a predictor of HCC recurrence in HCV-related chronic liver disease: a retrospective multicentric validation study. Dig Liver Dis 49:434–439. https://doi.org/10.1016/j.dld.2016.12.002

    Article  CAS  PubMed  Google Scholar 

  27. Kot M, Daniel WA (2008) The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: An in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochem Pharmacol 76:543–551. https://doi.org/10.1016/j.bcp.2008.05.025

    Article  CAS  PubMed  Google Scholar 

  28. Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF (1989) Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci U S A 86:7696–7700. https://doi.org/10.1073/pnas.86.20.7696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shimada T, Mernaugh RL, Guengerich FP (2005) Interactions of mammalian cytochrome P450, NADPH-cytochrome P450 reductase, and cytochrome b5enzymes. Arch Biochem Biophys 435:207–216. https://doi.org/10.1016/j.abb.2004.12.008

    Article  CAS  PubMed  Google Scholar 

  30. Sansen S, Yano JK, Reynald RL et al (2007) Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem 282:14348–14355. https://doi.org/10.1074/jbc.M611692200

    Article  CAS  PubMed  Google Scholar 

  31. Lynch T, Price A (2007) The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76:391–396

    Google Scholar 

  32. Qian L, Zolfaghari R, Ross a C, (2010) Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver. J Lipid Res 51:1781–1792. https://doi.org/10.1194/jlr.M002840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Waxman DJ, Attisano C, Guengerich FP, Lapenson DP (1988a) Human liver microsomal steroid metabolism: Identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263:424–436. https://doi.org/10.1016/0003-9861(88)90655-8

    Article  CAS  PubMed  Google Scholar 

  34. Fisher CDC, Lickteig AJA, Augustine LML et al (2009) Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 37:2087–2094. https://doi.org/10.1124/dmd.109.027466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Subramanian M, Low M, Locuson CW, Tracy TS (2009) CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis. Drug Metab Dispos 37:1682–1689. https://doi.org/10.1124/dmd.109.026500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fagerberg L, Hallström BM, Oksvold P et al (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics 13:397–406. https://doi.org/10.1074/mcp.M113.035600

    Article  CAS  PubMed  Google Scholar 

  37. Williams PA, Cosme J, Vinkovic DM et al (2004) Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305:683–686. https://doi.org/10.1126/science.1099736

    Article  CAS  PubMed  Google Scholar 

  38. Ward BA, Morocho A, Kandil A et al (2004) Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol 58:277–287. https://doi.org/10.1111/j.1365-2125.2004.02156.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Molowa DT, Schuetz EG, Wrighton SA et al (1986) Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci USA 83:5311–5315. https://doi.org/10.1073/pnas.83.14.5311

    Article  CAS  PubMed  Google Scholar 

  40. Korhonen T, Turpeinen M, Tolonen A et al (2008) Identification of the human cytochrome P450 enzymes involved in the in vitro biotransformation of lynestrenol and norethindrone. J Steroid Biochem Mol Biol 110:56–66. https://doi.org/10.1016/j.jsbmb.2007.09.025

    Article  CAS  PubMed  Google Scholar 

  41. Waxman DJ, Attisano C, Guengerich FP, Lapenson DP (1988b) Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263:424–436

    Article  CAS  Google Scholar 

  42. Nebert DW, Russell DW (2002) Clinical importance of the cytochromes P450. Lancet (London, England) 360:1155–1162. https://doi.org/10.1016/S0140-6736(02)11203-7

    Article  CAS  Google Scholar 

  43. Shi J, Geng MY, Liu CX (2004) Comparative studies of the effects of two novel sugar drug candidates on the CYP 1A2 and CYP 2E1 enzymes in different sexed rats using a “cocktail” approach. Molecules 9:978–987. https://doi.org/10.3390/91100978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Boshtam M, Asgary S, Kouhpayeh S et al (2017) Aptamers against pro- and anti-inflammatory cytokines: a review. Inflammation 40:340–349. https://doi.org/10.1007/s10753-016-0477-1

    Article  CAS  PubMed  Google Scholar 

  45. Christensen H, Hermann M (2012) Immunological response as a source to variability in drug metabolism and transport. Front Pharmacol 3:8. https://doi.org/10.3389/fphar.2012.00008

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shah P, Guo T, Moore DD, Ghose R (2014) Role of constitutive androstane receptor in toll-like receptor-mediated regulation of gene expression of hepatic drug-metabolizing enzymes and transporters. Drug Metab Dispos 42:172–181. https://doi.org/10.1124/dmd.113.053850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Aitken AE, Morgan ET (2007) Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos 35:1687–1693. https://doi.org/10.1124/dmd.107.015511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Aitken AE, Richardson TA, Morgan ET (2006) Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 46:123–149. https://doi.org/10.1146/annurev.pharmtox.46.120604.141059

    Article  CAS  PubMed  Google Scholar 

  49. De-Oliveira ACAX, Poça KS, Totino PRR, Paumgartten FJR (2015) Modulation of cytochrome P450 2A5 activity by lipopolysaccharide: low-dose effects and non-monotonic dose-response relationship. PLoS ONE 10:e0117842. https://doi.org/10.1371/journal.pone.0117842

    Article  PubMed  PubMed Central  Google Scholar 

  50. Schuck RN, Zha W, Edin ML et al (2014) The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease. PLoS ONE 9:e110162. https://doi.org/10.1371/journal.pone.0110162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Raffaele M, Bellner L, Singh SP et al (2019) Epoxyeicosatrienoic intervention improves NAFLD in leptin receptor deficient mice by an increase in HO-1-PGC1α mitochondrial signaling. Exp Cell Res 380:180–187. https://doi.org/10.1016/j.yexcr.2019.04.029

    Article  CAS  PubMed  Google Scholar 

  52. Yeboah MM, Hye Khan MA, Chesnik MA et al (2018) Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the pathogenesis of renal dysfunction in cirrhosis. Nephrol Dial Transplant 33:1333–1343. https://doi.org/10.1093/ndt/gfx354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhang C, Booz GW, Yu Q et al (2018) Conflicting roles of 20-HETE in hypertension and renal end organ damage. Eur J Pharmacol 833:190–200. https://doi.org/10.1016/j.ejphar.2018.06.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wu K-C, Lin C-J (2019) The regulation of drug-metabolizing enzymes and membrane transporters by inflammation: evidences in inflammatory diseases and age-related disorders. J Food Drug Anal 27:48–59. https://doi.org/10.1016/j.jfda.2018.11.005

    Article  CAS  PubMed  Google Scholar 

  55. Božina N, Bradamante V, Lovrić M (2009) Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 60:217–242. https://doi.org/10.2478/10004-1254-60-2009-1885

    Article  CAS  PubMed  Google Scholar 

  56. Venitt S (1994) Mechanisms of carcinogenesis and individual susceptibility to cancer. Clin Chem 40:1421–1425

    Article  CAS  Google Scholar 

  57. Nebert DW (1991) Role of genetics and drug metabolism in human cancer risk. Mutat Res 247:267–281

    Article  CAS  Google Scholar 

  58. Shaw G (2013) Polymorphism and single nucleotide polymorphisms (SNPs). BJU Int 112:664–665. https://doi.org/10.1111/bju.12298

    Article  PubMed  Google Scholar 

  59. Mochizuki J, Murakami S, Sanjo A et al (2005) Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma. J Gastroenterol Hepatol 20:1191–1197. https://doi.org/10.1111/j.1440-1746.2005.03808.x

    Article  CAS  PubMed  Google Scholar 

  60. Agundez J, a G, (2004) Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab 5:211–224. https://doi.org/10.2174/1389200043335621

    Article  CAS  PubMed  Google Scholar 

  61. Go RE, Hwang KA, Choi KC (2015) Cytochrome P450 1 family and cancers. J Steroid Biochem Mol Biol 147:24–30. https://doi.org/10.1016/j.jsbmb.2014.11.003

    Article  CAS  PubMed  Google Scholar 

  62. Ruparelia KC, Zeka K, Ijaz T et al (2018) The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells. Med Chem (Los Angeles) 14:322–332. https://doi.org/10.2174/1573406414666180112120134

    Article  CAS  Google Scholar 

  63. Johnson AL, Edson KZ, Totah RA, Rettie AE (2015) Cytochrome P450 ω-hydroxylases in inflammation and cancer. In: advances in pharmacology. Elsevier, London

    Book  Google Scholar 

  64. Jarrar YB, Lee S-J (2019) Molecular functionality of cytochrome P450 4 (CYP4) genetic polymorphisms and their clinical implications. Int J Mol Sci 20:4274. https://doi.org/10.3390/ijms20174274

    Article  CAS  PubMed Central  Google Scholar 

  65. Wang P, Zhang H, Zhang Z et al (2015) Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis. Onco Targets Ther 8:1175–1183. https://doi.org/10.2147/OTT.S80311

    Article  PubMed  PubMed Central  Google Scholar 

  66. Xiao Z, Shen J, Zhang L et al (2018) Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: recent progress and future prospects (Review). Oncol Lett 15:3395–3402. https://doi.org/10.3892/ol.2018.7758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  68. Gao J, Zhou J, He X-P et al (2016) Changes in cytochrome P450s-mediated drug clearance in patients with hepatocellular carcinoma in vitro and in vivo : a bottom-up approach. Oncotarget 7:28612–28623. https://doi.org/10.18632/oncotarget.8704

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zhou J, Wen Q, Li S et al (2016) Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma. Oncotarget 7:50612–50623. https://doi.org/10.18632/oncotarget.9437

    Article  PubMed  PubMed Central  Google Scholar 

  70. Tsunedomi R, Iizuka N, Hamamoto Y et al (2005) Patterns of expression of cytochrome P450 genes in progression of hepatitis C virus-associated hepatocellular carcinoma. Int J Oncol 27:661–667

    CAS  PubMed  Google Scholar 

  71. Zhang D, Lou J, Zhang X et al (2017) Hyperhomocysteinemia results from and promotes hepatocellular carcinoma via CYP450 metabolism by CYP2J2 DNA methylation. Oncotarget 8:15377–15392. https://doi.org/10.18632/oncotarget.14165

    Article  PubMed  Google Scholar 

  72. Samonakis DN, Koutroubakis IE, Sfiridaki A et al (2004) Hypercoagulable states in patients with hepatocellular carcinoma. Dig Dis Sci 49:854–858. https://doi.org/10.1023/B:DDAS.0000030099.13397.28

    Article  CAS  PubMed  Google Scholar 

  73. Sun CF, Haven TR, Wu TL et al (2002) Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta 321:55–62. https://doi.org/10.1016/S0009-8981(02)00092-X

    Article  CAS  PubMed  Google Scholar 

  74. Yan T, Lu L, Xie C et al (2015) Severely impaired and dysregulated cytochrome P450 expression and activities in hepatocellular carcinoma: implications for personalized treatment in patients. Mol Cancer Ther 14:2874–2886. https://doi.org/10.1158/1535-7163.MCT-15-0274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Blackburn HL, Ellsworth DL, Shriver CD, Ellsworth RE (2015) Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy. Cancer Causes Control 26:319–332. https://doi.org/10.1007/s10552-014-0519-7

    Article  PubMed  Google Scholar 

  76. Cardoso R, Lacerda P, Costa P et al (2017) Estrogen metabolism-associated CYP2D6 and IL6-174G/C polymorphisms in schistosoma haematobium infection. Int J Mol Sci 18:2560. https://doi.org/10.3390/ijms18122560

    Article  CAS  PubMed Central  Google Scholar 

  77. Oyama T (2005) Immunohistochemical evaluation of cytochrome P450 (CYP) and p53 in breast cancer. Front Biosci 10:1156. https://doi.org/10.2741/1608

    Article  CAS  PubMed  Google Scholar 

  78. Floriano-Sanchez E, Rodriguez NC, Bandala C et al (2014) CYP3A4 expression in breast cancer and its association with risk factors in Mexican women. Asian Pacific J Cancer Prev 15:3805–3809. https://doi.org/10.7314/APJCP.2014.15.8.3805

    Article  Google Scholar 

  79. Vaclavikova R, Hubackova M, Stribrna-Sarmanova J et al (2007) RNA expression of cytochrome P450 in breast cancer patients. Anticancer Res 27:4443–4450

    CAS  PubMed  Google Scholar 

  80. Parada H, Steck SE, Cleveland RJ et al (2017) Genetic polymorphisms of phase I metabolizing enzyme genes, their interaction with lifetime grilled and smoked meat intake, and breast cancer incidence. Ann Epidemiol 27:208-214.e1. https://doi.org/10.1016/j.annepidem.2016.11.005

    Article  PubMed  Google Scholar 

  81. Masson LF, Sharp L, Cotton SC, Little J (2005) Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review. Am J Epidemiol 161:901–915. https://doi.org/10.1093/aje/kwi121

    Article  CAS  PubMed  Google Scholar 

  82. Anttila S, Raunio H, Hakkola J (2011) Cytochrome P450-mediated pulmonary metabolism of carcinogens: regulation and cross-talk in lung carcinogenesis. Am J Respir Cell Mol Biol 44:583–590. https://doi.org/10.1165/rcmb.2010-0189RT

    Article  CAS  PubMed  Google Scholar 

  83. Hukkanen J, Pelkonen O, Hakkola J, Raunio H (2002) Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung. Crit Rev Toxicol 32:391–411

    Article  CAS  Google Scholar 

  84. Oyama T, Sugio K, Isse T et al (2008) Expression of cytochrome P450 in non-small cell lung cancer. Front Biosci 13:5787–5793

    Article  CAS  Google Scholar 

  85. Song N (2001) CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case-control study in China. Carcinogenesis 22:11–16. https://doi.org/10.1093/carcin/22.1.11

    Article  CAS  PubMed  Google Scholar 

  86. Fujita K (2006) Cytochrome P450 and anticancer drugs. Curr Drug Metab 7:23–37. https://doi.org/10.2174/138920006774832587

    Article  CAS  PubMed  Google Scholar 

  87. Reis M (2006) Farmacogenética aplicada ao câncer. Quimioterapia individualizada e especificidade molecular. Medicina (B Aires) 39:577–586. https://doi.org/10.11606/issn.2176-7262.v39i4p577-586

    Article  Google Scholar 

  88. Ingelman-Sundberg M (2004) Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 25:193–200. https://doi.org/10.1016/j.tips.2004.02.007

    Article  CAS  PubMed  Google Scholar 

  89. Tsuji D, Ikeda M, Yamamoto K et al (2016) Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients. Medicine (Baltimore) 95:e5151. https://doi.org/10.1097/MD.0000000000005151

    Article  CAS  PubMed Central  Google Scholar 

  90. Ahmed EM, EL-Maraghy SA, Teleb ZA, Shaheen AA (2014) Pretreatment with turmeric modulates the inhibitory influence of cisplatin and paclitaxel on CYP2E1 and CYP3A1/2 in isolated rat hepatic microsomes. Chem Biol Interact 220:25–32. https://doi.org/10.1016/j.cbi.2014.05.007

    Article  CAS  PubMed  Google Scholar 

  91. Kostrubsky VE, Lewis LD, Strom SC et al (1998) Induction of cytochrome P4503A by taxol in primary cultures of human hepatocytes. Arch Biochem Biophys 355:131–136. https://doi.org/10.1006/abbi.1998.0730

    Article  CAS  PubMed  Google Scholar 

  92. Kostrubsky VE, Ramachandran V, Venkataramanan R et al (1999) The use of human hepatocyte cultures to study the induction of cytochrome P-450. Drug Metab Dispos 27:887–894. https://doi.org/10.1109/MMCS.1997.609753

    Article  CAS  PubMed  Google Scholar 

  93. Li J, Li D, Tie C et al (2015) Cisplatin-mediated cytotoxicity through inducing CYP4A 11 expression in human renal tubular epithelial cells. J Toxicol Sci 40:895–900. https://doi.org/10.2131/jts.40.895

    Article  CAS  PubMed  Google Scholar 

  94. Chang TK, Weber GF, Crespi CL, Waxman DJ (1993) Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res 53:5629–5637

    CAS  PubMed  Google Scholar 

  95. Singh MS, Francis PA, Michael M (2011) Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes. The Breast 20:111–118. https://doi.org/10.1016/j.breast.2010.11.003

    Article  PubMed  Google Scholar 

  96. Thuy Phuong NT, Kim JW, Kim J-A et al (2017) Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the development of tamoxifen-resistant breast cancer. Oncotarget 8:71054–71069. https://doi.org/10.18632/oncotarget.20329

    Article  PubMed  PubMed Central  Google Scholar 

  97. Martinez VG, O’Connor R, Liang Y, Clynes M (2008) CYP1B1 expression is induced by docetaxel: effect on cell viability and drug resistance. Br J Cancer 98:564–570. https://doi.org/10.1038/sj.bjc.6604195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. McFadyen MCE, McLeod HL, Jackson FC et al (2001) Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance. Biochem Pharmacol 62:207–212. https://doi.org/10.1016/S0006-2952(01)00643-8

    Article  CAS  PubMed  Google Scholar 

  99. Brockdorff BL, Skouv J, Reiter BE, Lykkesfeldt AE (2000) Increased expression of cytochrome p450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines. Int J Cancer 88:902–906. https://doi.org/10.1002/1097-0215(20001215)88:6%3c902::AID-IJC10%3e3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  100. Horley NJ, Beresford KJM, Chawla T et al (2017) Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: overcoming cisplatin resistance in CYP1B1-overexpressing lines. Eur J Med Chem 129:159–174. https://doi.org/10.1016/j.ejmech.2017.02.016

    Article  CAS  PubMed  Google Scholar 

  101. Abraham JE, Maranian MJ, Driver KE et al (2010) CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen. Breast Cancer Res 12:R64. https://doi.org/10.1186/bcr2629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Blancas I, Rodriguez Gonzalez CJ, Muñoz-Serrano AJ et al (2018) Influence of CYP2D6 polymorphism in the outcome of breast cancer patients undergoing tamoxifen adjuvant treatment. J Clin Oncol 36:e12521–e12521. https://doi.org/10.1200/JCO.2018.36.15_suppl.e12521

    Article  Google Scholar 

  103. Lan B, Ma F, Zhai X et al (2018) The relationship between the CYP2D6 polymorphisms and tamoxifen efficacy in adjuvant endocrine therapy of breast cancer patients in Chinese Han population. Int J Cancer 143:184–189. https://doi.org/10.1002/ijc.31291

    Article  CAS  PubMed  Google Scholar 

  104. Chan CWH, Law BMH, So WKW et al (2020) Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen. J Cancer Res Clin Oncol 146:1395–1404. https://doi.org/10.1007/s00432-020-03206-w

    Article  CAS  PubMed  Google Scholar 

  105. Mwinyi J, Vokinger K, Jetter A et al (2014) Impact of variable CYP genotypes on breast cancer relapse in patients undergoing adjuvant tamoxifen therapy. Cancer Chemother Pharmacol 73:1181–1188. https://doi.org/10.1007/s00280-014-2453-5

    Article  CAS  PubMed  Google Scholar 

  106. Hassan M, Nilsson C, Olsson H et al (1999) The influence of interferon-alpha on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite in patients with multiple myeloma. Eur J Haematol 63:163–170

    Article  CAS  Google Scholar 

  107. Islam M, Frye RF, Richards TJ et al (2002) Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs. Clin Cancer Res 8:2480–2487

    CAS  PubMed  Google Scholar 

  108. Egbelakin A, Ferguson MJ, MacGill EA et al (2011) Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 56:361–367. https://doi.org/10.1002/pbc.22845

    Article  PubMed  Google Scholar 

  109. Deenen MJ, Cats A, Beijnen JH, Schellens JHM (2011) Part 2: Pharmacogenetic variability in drug transport and phase i anticancer drug metabolism. Oncologist 16:820–834. https://doi.org/10.1634/theoncologist.2010-0259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Marre F, Sanderink GJ, De Sousa G et al (1996) Hepatic biotransformation of docetaxel (Taxotere®) in vitro: Involvement of the CYP3A subfamily in humans. Cancer Res 56:1296–1302

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  112. Relling MV, Nemec J, Schuetz EG et al (1994) O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol Pharmacol 45:352–358

    CAS  PubMed  Google Scholar 

  113. Shet MS, McPhaul M, Fisher CW et al (1997) Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 25:1298–1303

    CAS  PubMed  Google Scholar 

  114. Makowsky GS (2015) Advances in clinical chemistry, Volume 71. Elsevier, 225 Wyman Street, Waltham, MA 02451, USA 525 B Street, Suite,1800 San Diego, CA 92101–4495, USA 125 London Wall, London, EC2Y 5AS. UK The Boulevard, Langford Lane, Kidlington, Oxford, UK

    Google Scholar 

  115. Chugh R, Wagner T, Griffith KA et al (2007) Assessment of ifosfamide pharmacokinetics, toxicity, and relation to CYP3A4 activity as measured by the erythromycin breath test in patients with sarcoma. Cancer 109:2315–2322. https://doi.org/10.1002/cncr.22669

    Article  CAS  PubMed  Google Scholar 

  116. Peng B, Lloyd P, Schran H (2005) Clinical pharmacokinetics of imatinib. Clin Pharmacokinet 44:879–894. https://doi.org/10.2165/00003088-200544090-00001

    Article  CAS  PubMed  Google Scholar 

  117. Cresteil T, Monsarrat B, Alvinerie P et al (1994) Taxol metabolism by human liver microsomes: identification of cytochrome P450 isozymes involved in its biotransformation. Cancer Res 54:386–392

    CAS  PubMed  Google Scholar 

  118. Rahman A, Korzekwa KR, Grogan J et al (1994) Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543–5546

    CAS  PubMed  Google Scholar 

  119. Gong L, Giacomini MM, Giacomini C et al (2017) PharmGKB summary. Pharmacogenet Genomics 27:240–246. https://doi.org/10.1097/FPC.0000000000000279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Kobayakawa M, Kojima Y (2011) Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies. Onco Targets Ther 4:193. https://doi.org/10.2147/OTT.S19059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sulkes A, Benner SE, Canetta RM (1998) Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer. J Clin Oncol 16:3461–3475. https://doi.org/10.1200/JCO.1998.16.10.3461

    Article  CAS  PubMed  Google Scholar 

  122. Chhetri P (2016) Current development of anti-cancer drug S-1. J Clin Diagnostic Res 10:XE01–XE05. https://doi.org/10.7860/JCDR/2016/19345.8776

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank Michael Arends for editing the manuscript.

Funding

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Financial code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Process 305787/2018–7).

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  1. Department of Pharmacology, Federal University of Paraná, PO Box 19031, CuritibaCuritiba, PR, 81531-980, Brazil

    Maria Carolina Stipp & Alexandra Acco

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MCS was responsible for conceptualization, literature review and writing; AA was responsible for the manuscript format, writing and editing.

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Stipp, M.C., Acco, A. Involvement of cytochrome P450 enzymes in inflammation and cancer: a review. Cancer Chemother Pharmacol 87, 295–309 (2021). https://doi.org/10.1007/s00280-020-04181-2

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