The impact of Catechol-O-methyl transferase knockdown on the cell proliferation of hormone-responsive cancers

Tolba, Mai F.; Omar, Hany A.; Hersi, Fatema; Nunes, Ane Cláudia Fernandes; Noreddin, Ayman M.

doi:10.1016/j.mce.2019.03.007

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…A similar effect was observed in vivo as COMT-expressing cells inhibited xenograft tumor growth. In concordance, by silencing COMT in LNCaP cells, we observed decreased apoptosis and accelerated migration capability and a recent report by Tolba et al [37] also showed COMT silencing could enhance proliferation of PC3 cells. This tumor suppressive effect of COMT is also shown in other cancers such as pancreatic [36] and colorectal [38]; and in a prior study done in our laboratory, COMT significantly reduced proliferation of renal cancer cells treated with 4-hydroxyestradiol as compared to vector control [33].…”

Section: Plos Onesupporting

confidence: 92%

“…In 4-hydroxyestradiol stimulated renal cancer cells, COMT caused increased apoptosis along with increased GADD45a levels [33]. Aside from apoptosis-related genes, COMT can play a protective role by affecting other pathway genes such as ER-α, p21cip1, p27kip1, NF-κB (P65) and CYP19A1 in prostate cancer [37], cause a reduction in p-AKT, mutant p53, and cyclin D1 but an increase in p-GSK3-b, PTEN and E-cadherin in pancreatic cancer cells [36], and cause inhibition of p-AKT but increased PTEN, p53, p27, and E-Cadherin in colorectal cancer cells [38].…”

Section: Plos Onementioning

confidence: 99%

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Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

et al. 2021

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Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer.

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Section: Plos Onesupporting

confidence: 92%

Section: Plos Onementioning

confidence: 99%

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

et al. 2021

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“…In accordance with our results, other studies concluded that polymorphism in COMT gene, which codes for a low activity variant of COMT enzyme, is associated with increased risk of breast cancer development [24][25][26][27][28].…”

Section: Discussionsupporting

confidence: 92%

Relationship between 17β estradiol (17βE) levels and Catechol -O- methyltransferase (COMT) levels in ovarian cancers

El-Etreby¹,

Badawy²,

H³

et al. 2021

EJGO

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Objectives: Epidemiological data show that induction of ovarian cancer is related to estrogen exposure and metabolism. In addition catechol metabolites of estrogen also contribute to carcinogenesis. O methylation by Catechol -O-methyltransferase is a phase II metabolic inactivation pathway for catechol estrogens. The goal of this study was to evaluate a potential correlation between COMT and 17β estradiol levels and ovarian cancer. Subjects and methods: COMT and 17βE levels were measured in ovarian tissue and serum from 80 subjects: 30 with malignant ovarian tumors, 30 with benign ovarian tumors and 20 healthy controls. Results: Tissue and serum levels of Catechol -O-methyltransferase and 17β estradiol were determined using enzyme linked immunosorbant assay. According to our results Catechol -O-methyltransferase inhibition in the malignant group was associated with high levels of 17β estradiol, while in benign group high levels of COMT was associated with low levels of 17β estradiol in both serum and tissue homogenates. Conclusions: Low level of COMT and high tissue/serum levels of 17β estradiol may be contributory factors for the development of ovarian cancer. This supports the notion that targeting the metabolism of estrogen can be another way to reduce ovarian cancer risk.

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“…Prostate cancer is a very common cause of death in men patients; [ 60 ] however, nonmetastasized cancer has a better prognosis and lower risk than metastasized cancer, most commonly the tumor will metastasize to bone and regional lymph nodes. Recent studies suggest that alkaline phosphatase and bone‐specific alkaline phosphatase enzymes are important parameters to be considered as they improve the prognosis.…”

Section: The Significance Of Aps In Several Physiological Conditions mentioning

confidence: 99%

Recent advances with alkaline phosphatase isoenzymes and their inhibitors

Zaher

El‐Gamal

Omar

et al. 2020

Archiv der Pharmazie

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Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphatecontaining physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in the last 5 years (between 2015 and 2019). K E Y W O R D S alkaline phosphatase, inhibitors, isoenzymes, structure-activity relationship

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The impact of Catechol-O-methyl transferase knockdown on the cell proliferation of hormone-responsive cancers

Cited by 16 publications

References 46 publications

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

Relationship between 17β estradiol (17βE) levels and Catechol -O- methyltransferase (COMT) levels in ovarian cancers

Recent advances with alkaline phosphatase isoenzymes and their inhibitors

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