Exploring glyoxalase 1 expression in prostate cancer tissues: Targeting the enzyme by ethyl pyruvate defangs some malignancy‐associated properties

Baunacke, Martin; Horn, Lars‐Christian; Trettner, Susanne; Engel, Kathrin M.; Hemdan, Nasr Y. A.; Wiechmann, Volker; Stolzenburg, Jens‐Uwe; Bigl, Marina; Birkenmeier, Gerd

doi:10.1002/pros.22728

Cited by 38 publications

(44 citation statements)

References 49 publications

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“…Studies have shown that high expression of GLO1 in gastric cancer promotes tumor cell growth and proliferation, and enhances transcriptional activities of NF-κB and AP-1 [20,21]. Since a positive correlation between the level of GLO1 in prostate cancer tissues and the rate of cell proliferation was found, we considered that GLO1 may represent a risk factor for the development and progression of prostate cancer [22]. GLOI has also been shown to serve as a pro-survival factor in invasive prostate cancer PC3 cells by eluding apoptosis through the NF-κB signaling pathway [23].…”

Section: Role Of Gloi In Tumor Development and Progressionmentioning

confidence: 99%

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

Geng

Ma²,

Zhang³

et al. 2014

Oncol Res Treat

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SummaryGlyoxalase I (GLO1) belongs to the glyoxalase system, which catalyzes the conversion of deleterious methylglyoxal, mainly produced by glycolysis, to non-toxic D-lactate. The expression of GLO1 was up-regulated in tumor tissues with high metabolic rate, whereas inhibition of GLO1 expression led to the accumulation of glyoxal and methylglyoxal, significantly inducing cell damage or apoptosis. This suggests that GLO1 may play an important role in tumor cell proliferation and survival, and may represent a potential therapeutic target for tumors. Moreover, overexpression of GLO1 was associated with multidrug resistance in cancer chemotherapy. This review describes the role of GLO1 in tumor cell proliferation and survival, and the potential of GLO1 as a biomarker for tumor diagnosis and as a target for anticancer drug development.

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Section: Role Of Gloi In Tumor Development and Progressionmentioning

confidence: 99%

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

Geng

Ma²,

Zhang³

et al. 2014

Oncol Res Treat

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“…Notably, a distinctly high activity of Glo1 was observed in 22 out of 22 PCa specimens and none to little activity in 10 out of 10 non-malignant specimens. Although preliminary, these results opened new pathways of investigation towards the study of Glo1 expression, either at mRNA, protein or functional level, in PCa tissues and normal counterparts or in differently aggressive and invasive PCas [36,37,[52][53][54][55]. Overall, these studies strongly indicated Glo1 as a novel important protein involved in PCa genesis and progression, thus suggesting an oncogenic role for this enzyme in this neoplasm.…”

Section: Glo1mentioning

confidence: 96%

“…More recently, it has been also reported that curcumin inhibits Glo1 with the consequent intracellular accumulation of non-tolerable levels of MG and GSH, that, by modulating various metabolic cellular pathways, hamper malignant cells growth [64]. Finally, more recently, Baunacke et al [53] identified ethyl pyruvate as agent targeting Glo1 and defanging some malignancy-associated properties of PCa cells and Valenti et al [65] found that 3-bromopyruvate induced rapid human PCa cell death by affecting, among the others, Glo1.…”

Section: Glo1mentioning

confidence: 98%

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Glyoxalases in Urological Malignancies

Antognelli¹,

Talesa²

2017

Preprint

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Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.

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“…Mouse studies have demonstrated that its overexpression can reduce AGE production and oxidative damage associated with hyperglycaemia [99], thus demonstrating a direct link between methylglyoxal and these pathologies. Glyoxalase is upregulated in association with rapid cell proliferation [100] and also in association with some cancers, including gastric cancer [101] and prostate cancer [102] (gastric cancer is the second highest cause of cancer-related mortality worldwide [103]). Overexpression of glyoxalase I is associated with increased gastric wall invasion and lymph node metastasis [101].…”

Section: Glyoxal Methylglyoxal and Glyoxylatementioning

confidence: 99%