Department of Pharmacology, Federal University of Paraná, PO Box 19031, CuritibaCuritiba, PR, 81531-980, Brazil.
Cancer Chemother Pharmacol. 2021 Mar;87(3):295-309. doi: 10.1007/s00280-020-04181-2. Epub 2020 Oct 28.
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.
细胞色素 P450(CYP)酶负责药物、外源性物质和内源性物质的生物转化。这种酶活性可以被内在和外在因素调节,从而改变机体对药物的反应。负责酶抑制或诱导的因素之一是巨噬细胞、淋巴细胞和中性粒细胞释放促炎细胞因子,如白细胞介素-1(IL-1)、IL-6、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)。这些细胞也存在于肿瘤微环境中,参与癌症的发展,癌症是一种以促进细胞存活和增殖的细胞突变为特征的疾病。CYP 酶也会发生突变,导致酶的多态性和活性的调节。因此,肿瘤微环境中的促炎细胞因子对 CYP 酶的抑制或诱导会促进癌变,并影响化疗,导致不良反应、毒性或治疗失败。本综述通过回顾体外、体内和临床研究,讨论了 CYP 在肝癌、乳腺癌、肺癌和化疗中的相关性。我们还讨论了阐明炎症、CYP 和癌症之间的关系以预测药物相互作用和治疗效果的重要性。