CYP1B1 gene: Implications in glaucoma and cancer

Alsubait, Arwa; Aldossary, Wadha; Rashid, Mamoon; Algamdi, Amani; Alrfaei, Bahauddeen M.

doi:10.7150/jca.42669

Cited by 35 publications

(22 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, the constitutively overexpressed CYP1B1 in cancer cells and the tumor microenvironment may be used to design anti-cancer prodrugs activated by this enzyme. Another pathway of CYP1B1 studies concerns the relation between mutations of the CYP1B1 gene and the occurrence of eye diseases [9,10] and cardiovascular disorders [11] (Figure 1). CYP1s are induced by agonists of the aryl hydrocarbon receptor (AhR), includin polychlorinated dioxins with strong inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD and polycyclic aromatic hydrocarbons [12,13].…”

Section: Introductionmentioning

confidence: 99%

New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

Mikstacka

Dutkiewicz

2021

Processes

View full text Add to dashboard Cite

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic heme-containing monooxygenase. CYP1B1 contributes to the oxidative metabolism of xenobiotics, drugs, and endogenous substrates like melatonin, fatty acids, steroid hormones, and retinoids, which are involved in diverse critical cellular functions. CYP1B1 plays an important role in the pathogenesis of cardiovascular diseases, hormone-related cancers and is responsible for anti-cancer drug resistance. Inhibition of CYP1B1 activity is considered as an approach in cancer chemoprevention and cancer chemotherapy. CYP1B1 can activate anti-cancer prodrugs in tumor cells which display overexpression of CYP1B1 in comparison to normal cells. CYP1B1 involvement in carcinogenesis and cancer progression encourages investigation of CYP1B1 interactions with its ligands: substrates and inhibitors. Computational methods, with a simulation of molecular dynamics (MD), allow the observation of molecular interactions at the binding site of CYP1B1, which are essential in relation to the enzyme’s functions.

show abstract

Section: Introductionmentioning

confidence: 99%

New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

Mikstacka

Dutkiewicz

2021

Processes

View full text Add to dashboard Cite

show abstract

“…While low amounts of CYP1B1 mRNA can be detected in the liver (Chang et al, 2001), the CYP1B1 protein is primarily expressed in extrahepatic tissues, including breast, prostate, ovary, kidney and lungs (Tang et al, 1996, Spink et al, 1998Spivack et al, 2001). Due to its role in metabolizing steroid hormones and fatty acids that stimulate growth of cancer cells (Badawi, 2001;Alsubait, 2020), CYP1B1 has been a target for therapeutic inhibition (Li et al, 2017). Particular Cyp1B1 allelic variants, which confer decreased enzymatic activity, are highly penetrant in conferring pediatric glaucoma (Falero-Perez et al, 2019), indicating a role in ocular development.…”

Section: Environmental and Molecular Mutagenesismentioning

confidence: 99%

CYP1B1 converts procarcinogens into genotoxins in Saccharomyces cerevisiae

Kannan

Perpetua

Dolan

et al. 2021

Preprint

View full text Add to dashboard Cite

CYP1B1 activates many chemical carcinogens into potent genotoxins, and allelic variants are risk factors in lung, breast, and prostate cancer. However, genetic instability phenotypes incurred by CYP1B1-activated metabolites have been investigated for only few compounds. In this study, we expressed human CYP1B1 in yeast strains that measure DNA damage-associated toxicity and frequencies of chromosomal translocations and mutations. DNA damage-associated toxicity was measured in a rad4 rad51 strain, defective in both DNA excision and recombinational repair. Frequencies of chromosomal translocations were measured in diploid yeast strains containing two his3 fragments, and mutation frequencies were measured by selecting for canavanine resistance (CanR) in haploid strains. These strains were exposed to benzo[a]pyrene dihydrodiol (BaP-DHD), aflatoxin B1 (AFB1), and the heterocyclic aromatic amines, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ). We observed that AFB1, BaP-DHD, IQ, and MeIQx conferred toxicity in the DNA repair mutant expressing CYP1B1. Translocation frequencies increased eight-fold and three-fold after exposure to 50 μM AFB1 and 33 μM BaP-DHD respectively. Only a two-fold increase in mutation frequency was observed after exposure to 50 μM AFB1. However, a robust DNA damage response was observed after AFB1 exposure, as measured by the induction of the small subunit of ribonucleotide reductase, Rnr3. While CYP1B1-mediated activation of BaP-DHD and heterocyclic aromatic amines was expected, strong activation of AFB1 was not. These studies demonstrate that CYP1B1-mediated activation of carcinogens does not only activate compounds to become mutagens but also can convert compounds to become potent recombinagens.

show abstract

“…Several metabolic enzymes, particularly members of the cytochrome P450 (CYP) superfamily, are being investigated for their potential role in tumor malignancy [6][7][8]. Of recent interest is a novel member of the CYP1 gene family, CYP1B1, which is an extrahepatic enzyme that is engaged in the metabolism of several endogenous and xenobiotic compounds [9]. CYP1B1 has been implicated in the oxidation of steroids, particularly estrogen and melatonin.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study

et al. 2021

View full text Add to dashboard Cite

Background Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. Objective The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme’s relationship with several clinicopathological features. Methods Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. Results CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). Conclusions The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.

show abstract

CYP1B1 gene: Implications in glaucoma and cancer

Cited by 35 publications

References 54 publications

New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

CYP1B1 converts procarcinogens into genotoxins in Saccharomyces cerevisiae

Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study

Contact Info

Product

Resources

About