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
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The authors thank Michael Arends for editing the manuscript.
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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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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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DOI: https://doi.org/10.1007/s00280-020-04181-2