The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of cytochrome P450 enzymes including CYP1B1 and thus plays a pivotal role for initiating cancer and its progression.
This study may provide a good starting point for the further development of more potent multi-functional agents with CYP1B1 inhibitory activity and cytotoxic potency in cancer prevention and treatment.
During late 1990s, two findings renewed the interest on phytoestrogens as means to control hormone induced cancer: (i) revelation of overexpression of CYP1B1 in breast & ovarian cancer and (ii) protection offered by alphanapthoflavone (ANF) against hormone induced cancer.
In order to characterize the cellular functions of CYP1B1 associated with cancer cell survival, the relationship between this oncogene and death receptor 4 (DR4) was determined.
This study revealed that TAX might be able to act as a chemotherapeutic agent against CYP1A1- and CYP1B1-mediated cancer and the inhibition of the DMBA-induced mammary carcinogenesis in a rat model.<b>Abbreviations used:</b> CYPs: Cytochrome P450s; PAH: polycyclic aromatic hydrocarbons; HRP- Horseradish peroxidase; BSA: Bovine serum albumin; DTTP: Deoxythymidine Triphosphate (nucleotide); RT-qPCR: Real Time quantitative polymerase chain reaction; CADD: Computer Aided Drug Drafting.
Accumulating evidence indicates that modulation of CYP1B1 can decrease adipogenesis and tumorigenesis, and prevent obesity, hypertension, atherosclerosis, and cancer.
This study highlights the critical role of CYP1B1 and AhR in TCDD activity and proposes that inhibition of these key molecules might serve as a potential therapeutic approach for treatment of allergy and cancer.
These potent cell-permeable and water-soluble CYP1B1 inhibitors are likely to have useful roles in the treatment of cancer, glaucoma, ischemia and obesity.
In the present study, we evaluated whether the G protein estrogen receptor namely GPER may provide an alternate route toward the expression and function of CYP1B1 in ER-negative breast cancer cells, in main players of the tumor microenvironment as cancer associated fibroblasts (CAFs) that were obtained from breast cancer patients, in CAFs derived from a cutaneous metastasis of an invasive mammary ductal carcinoma and in breast tumor xenografts.
Because of demonstrated unequivocal involvement in smoking-induced cancer in laboratory animals, four candidate genes--AHR, CYP1A1, CYP1A2, and CYP1B1--were selected for a clinical genotype-phenotype association study of HNSCC risk in smokers.
We performed a detailed search using the PubMed and EMBASE libraries to obtain all relevant published reports on the relationship between the G119T and A453G polymorphisms in CYP1B1 and cancer risk.
To derive a more precise estimation of the association between the CYP1B1 polymorphisms and cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP1B1Leu432Val, Asn453Ser, Arg48Gly, and Ala119Ser polymorphisms.
A case-control study involving 750 cases with squamous-cell carcinoma of the head and neck (HNSCC) and an equal number of healthy controls was initiated to investigate the association of polymorphisms in the drug metabolizing genes cytochrome P450 1A1 (CYP1A1), CYP1B1, CYP2E1 and glutathione S-transferase M1 (GSTM1) with the risk of developing cancer.
The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation.
However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis.
The study reveals active CYP1 overexpression in human tumors and uncovers the potential use of CYP1 enzymes and mainly CYP1B1 as targets for cancer therapy.
Recently, large studies on the association between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease.