Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Al-saraireh, Yousef M.; Alshammari, Fatemah O F O; Youssef, Ahmed M M; Al-Sarayreh, Sameeh; Almuhaisen, Ghadeer H; Alnawaiseh, Nedal; Alrawashdeh, Hamzeh Mohammad; Al-Shuneigat, Jehad

doi:10.21203/rs.3.rs-128233/v1

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…AhR induces expression of AhRR in a tissue-specific manner, which in turn inhibits AhR -induced expression of certain genes through different mechanisms [ 50 , 51 ]. Those genes include common predictors across all targets including the insulin-like growth factor binding protein-5 (IFGBp-5), the Lysyl Oxidase (LOX), and the Cytochrome P450 CYP1B1 which are thought to contribute to malignant transformation in different types of tissues [ 52 , 53 , 54 , 55 , 56 ]. Throughout these common predictor genes, AhR mediates gene expression in many pathways involved in development and progression of cancer; this includes the matrix metalloproteinase-9 ( MMP-9 ) through the c-Jun-dependent pathway, the ERK-FAK-Rac-1 pathway, as well as the Snail superfamily transcriptional repressor-1 (Snail-1), the TWIST family of basic helix-loop-helix transcription factors Twist1 and Twist2, and vimentin in the E-cadherin-related pathways [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

AhRR methylation contributes to disease progression in urothelial bladder cancer

El-Haddad

Kawak

Asmar

et al. 2022

CBM

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BACKGROUND: Bladder Cancer (BCa) is the tenth most incidental malignancy worldwide. BCa is mostly attributed to environmental exposure and lifestyle, particularly tobacco smoking. The Aryl Hydrocarbon Receptor Repressor (AhRR) participates in the induction of many enzymes involved in metabolizing carcinogens, including tobacco smoke components. Additionally, studies have shown that smoking demethylates the (AhRR) gene in blood, suggesting AhRR demethylation as a specific serum smoking biomarker. OBJECTIVE: This study aimed to validate AhRR demethylation as a smoking biomarker in the target tissue and investigate its contribution to bladder carcinogenesis. METHODS: AhRR percent methylation was tested for its association with patient smoking status and oncogenic outcome indicators, particularly p53, RB1, and FGFR3 activating mutations, muscle-invasiveness, and tumor grade, in 180 BCa tissue-based DNA. RESULTS: Results showed significantly higher AhRR percent methylation in muscle-invasive compared to non-muscle invasive tumors (42.86% vs. 33.98%; p= 0.011), while lower AhRR methylation was significantly associated with FGFR3 Codon 248 mutant genotype compared to wild-type (28.11% ± 9.44 vs. 37.87% ± 22.53; p= 0.036). All other tested associations were non-statistically significant. CONCLUSIONS: Although AhRR methylation did not predict smoking status in BCa tumors, it seems to play a role in carcinogenesis and disease progression. Our findings make a basis for further research.

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Section: Discussionmentioning

confidence: 99%

AhRR methylation contributes to disease progression in urothelial bladder cancer

El-Haddad

Kawak

Asmar

et al. 2022

CBM

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“…The level of cytotoxicity of the methanol extract of R. mucronata was categorized using the Geran protocol and the protocol described by the National Cancer Institute (NCI) of the United States as a highly cytotoxic substance (IC50 < 20 µ g/mL), a moderately cytotoxic substance (IC50 of 21-200 µ g/mL), a weakly cytotoxic substance (IC50 of 201-500 µ g/mL), or a non-cytotoxic substance (IC50 > 501 µ g/mL) [42,43].…”

Section: 4 Criteria For Anticancer Effect Levelsmentioning

confidence: 99%

“…The ratio of a plant extract's IC50 value in a non-cancer cell line (WI-38) to its IC50 value in each cancer cell line is known as the selectivity index. SI values below three indicate that the extract is not selective in relation to non-cancer cells [42,43]. The selectivity indices of the methanol extract were determined using Equation ( 2):…”

Section: Selectivity Indexmentioning

confidence: 99%

Phytochemistry and Anticancer Effects of Mangrove (Rhizophora mucronata Lam.) Leaves and Stems Extract against Different Cancer Cell Lines

2022

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The biologically active components of the methanol extracts of R. mucronata were identified using GC/MS. The anticancer effects of each methanol extract from the leaves and stem were evaluated against cancer and non-cancer cell lines. The MTT assay was used in order to evaluate cell viability, and the IC50 and the selectivity indices were calculated in relation to a positive control (doxorubicin). The results showed that 11 and 8 different chemical compounds were found in the methanol extracts from the leaves and stems of R. mucronata, respectively. The active constituents of R. mucronata leaves and stems had anticancer effects against colon cancer (CaCo-2), with IC50 levels of 127 ± 4 μg/mL and 107 ± 6 μg/mL, respectively, and on breast cancer (MCF-), with IC50 levels of 158 ± 10 μg/mL and 138 ± 4 μg/mL, respectively. These were both greater than their effects on prostate cancer (PC-3), for which they showed IC50 levels of 480 ± 14 μg/mL and 294 ± 3 μg/mL, respectively. However, the anticancer effect of the stems on lung cancer (A549) (IC50 = 155 ± 10 μg/mL) was greater than that of the leaves (IC50 = 376 ± 9 μg/mL) in comparison with doxorubicin. Neither the stems nor the leaves of R. mucronata showed any cytotoxicity against normal cells (WI-38), with the IC50 being 932 ± 30 μg/mL for the leaves and 629 ± 3 μg/mL for the stems.

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

Alshammari¹,

Al-saraireh²,

Youssef³

et al. 2021

Preprint

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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.

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Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Cited by 3 publications

References 24 publications

AhRR methylation contributes to disease progression in urothelial bladder cancer

AhRR methylation contributes to disease progression in urothelial bladder cancer

Phytochemistry and Anticancer Effects of Mangrove (Rhizophora mucronata Lam.) Leaves and Stems Extract against Different Cancer Cell Lines

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

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