Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 3/2021

01-03-2021 | Lung Cancer | Review Article

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

Authors: Maria Carolina Stipp, Alexandra Acco

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2021

Login to get access

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.
Literature
2.
go back to reference Christmas P (2015) Role of cytochrome P450s in inflammation. In: advances in pharmacology. Elsevier, LondonCrossRef Christmas P (2015) Role of cytochrome P450s in inflammation. In: advances in pharmacology. Elsevier, LondonCrossRef
6.
go back to reference Guengerich F (2014) Analysis and characterization of enzymes and nucleic acids relevant to toxicology. In: Hayes’ principles and methods of toxicology. CRC Press, NewyorkCrossRef Guengerich F (2014) Analysis and characterization of enzymes and nucleic acids relevant to toxicology. In: Hayes’ principles and methods of toxicology. CRC Press, NewyorkCrossRef
9.
go back to reference Furge LL, Guengerich FP (2006) Cytochrome P450 enzymes in drug metabolism and chemical toxicology: an introduction. Biochem Mol Biol Educ 34:66–74CrossRef Furge LL, Guengerich FP (2006) Cytochrome P450 enzymes in drug metabolism and chemical toxicology: an introduction. Biochem Mol Biol Educ 34:66–74CrossRef
10.
go back to reference Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 239:2379–2385CrossRef Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 239:2379–2385CrossRef
12.
go back to reference Van der Weide J, Steijns LS (1999) Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 36(Pt 6):722–729CrossRef Van der Weide J, Steijns LS (1999) Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 36(Pt 6):722–729CrossRef
21.
go back to reference 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 63:6532–6536PubMed 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 63:6532–6536PubMed
31.
go back to reference Lynch T, Price A (2007) The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76:391–396 Lynch T, Price A (2007) The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76:391–396
41.
go back to reference 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 263:424–436CrossRef 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 263:424–436CrossRef
56.
go back to reference Venitt S (1994) Mechanisms of carcinogenesis and individual susceptibility to cancer. Clin Chem 40:1421–1425CrossRef Venitt S (1994) Mechanisms of carcinogenesis and individual susceptibility to cancer. Clin Chem 40:1421–1425CrossRef
57.
go back to reference Nebert DW (1991) Role of genetics and drug metabolism in human cancer risk. Mutat Res 247:267–281CrossRef Nebert DW (1991) Role of genetics and drug metabolism in human cancer risk. Mutat Res 247:267–281CrossRef
63.
go back to reference Johnson AL, Edson KZ, Totah RA, Rettie AE (2015) Cytochrome P450 ω-hydroxylases in inflammation and cancer. In: advances in pharmacology. Elsevier, LondonCrossRef Johnson AL, Edson KZ, Totah RA, Rettie AE (2015) Cytochrome P450 ω-hydroxylases in inflammation and cancer. In: advances in pharmacology. Elsevier, LondonCrossRef
70.
go back to reference 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 27:661–667PubMed 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 27:661–667PubMed
79.
go back to reference Vaclavikova R, Hubackova M, Stribrna-Sarmanova J et al (2007) RNA expression of cytochrome P450 in breast cancer patients. Anticancer Res 27:4443–4450PubMed Vaclavikova R, Hubackova M, Stribrna-Sarmanova J et al (2007) RNA expression of cytochrome P450 in breast cancer patients. Anticancer Res 27:4443–4450PubMed
83.
go back to reference 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 32:391–411CrossRef 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 32:391–411CrossRef
84.
go back to reference Oyama T, Sugio K, Isse T et al (2008) Expression of cytochrome P450 in non-small cell lung cancer. Front Biosci 13:5787–5793CrossRef Oyama T, Sugio K, Isse T et al (2008) Expression of cytochrome P450 in non-small cell lung cancer. Front Biosci 13:5787–5793CrossRef
94.
go back to reference 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 53:5629–5637PubMed 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 53:5629–5637PubMed
106.
go back to reference 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 63:163–170CrossRef 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 63:163–170CrossRef
107.
go back to reference 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 8:2480–2487PubMed 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 8:2480–2487PubMed
110.
go back to reference 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 56:1296–1302PubMed 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 56:1296–1302PubMed
112.
go back to reference Relling MV, Nemec J, Schuetz EG et al (1994) O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol Pharmacol 45:352–358PubMed Relling MV, Nemec J, Schuetz EG et al (1994) O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol Pharmacol 45:352–358PubMed
113.
go back to reference Shet MS, McPhaul M, Fisher CW et al (1997) Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 25:1298–1303PubMed Shet MS, McPhaul M, Fisher CW et al (1997) Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 25:1298–1303PubMed
114.
go back to reference 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 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
117.
go back to reference 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 54:386–392PubMed 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 54:386–392PubMed
118.
go back to reference Rahman A, Korzekwa KR, Grogan J et al (1994) Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543–5546PubMed Rahman A, Korzekwa KR, Grogan J et al (1994) Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543–5546PubMed
Metadata
Title
Involvement of cytochrome P450 enzymes in inflammation and cancer: a review
Authors
Maria Carolina Stipp
Alexandra Acco
Publication date
01-03-2021
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-020-04181-2

Other articles of this Issue 3/2021

Cancer Chemotherapy and Pharmacology 3/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine