Glyoxalase I Activity in Human Prostate Cancer: A Potential Marker and Importance in Chemotherapy

Davidson, Scott D.; Cherry, James; Choudhury, Muhammad; Tazaki, Hiroshi; Mallouh, Camille; Konno, Sensuke

doi:10.1016/s0022-5347(01)61996-7

Cited by 57 publications

(27 citation statements)

References 9 publications

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“…Another study by Di Ilio et al [32] measured glyoxalase I and glyoxalase II activities in urogenital tumor and non-tumorous tissues and found decreased glyoxalase I levels in 10 out of 15 kidney tumors when compared with corresponding normal kidney tissue. Elevated levels of glyoxalase I were also reported in human prostate cancer [33]. Studies from Ranganathan et al [34] showed elevations in glyxalase I activities in 16 out of 21 colon tumor samples as compared to corresponding normal colon tissues.…”

Section: Discussionmentioning

confidence: 91%

Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

Wan

et al. 2001

Cell Res

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Using a combination of hybridization of PAC to a cDNA library and RACE technique, we isolated a novel cDNA, designated as C17orf25 (Chromosome 17 open reading frame 25, previously named it HC71A), from the deletion region on chromosome 17p13.3. The cDNA encodes a protein of 313 amino acids with a calculated molecular mass of 34.8 kDa. C17orf25 is divided into 10 exons and 9 introns, spanning 23 kb of genomic DNA. Northern blot analysis showed that the mRNA expression of C17orf25 was decreased in hepatocellular carcinoma samples as compared to adjacent noncancerous liver tissues from the same patients. The transfection of C17orf25 into the hepatocellular carcinoma cell SMMC7721 and overexpression could inhibit the cell growth. The above results indicate that C17orf25 is a novel human gene, and the cloning and preliminary characterization of C17orf25 is a prerequisite for further functional analysis of this novel gene in human hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 91%

Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

Wan

et al. 2001

Cell Res

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“…9,10 Abnormal expression of this system has been demonstrated in a number of cellular disorders, including cancer. [11][12][13][14][15] In particular, altered expression and activities of GI and GII have been documented in tumor urogenital tissues [12][13][14][15][16][17] and in prostate tumor cell lines compared with corresponding normal tissues. 18 These alterations are considered to be crucial for sustaining tumor viability/survival under an altering microenvironment with tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

Antognelli

Buono²,

Baldracchini³

et al. 2007

Cancer Biology & Therapy

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Glyoxalase system, a ubiquitous detoxification pathway protecting against cellular damage caused by potent cytotoxic metabolites, is involved in the regulation of cellular growth. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Recently, we described a possible regulatory effect by estrogens on glyoxalase genes in human breast cancer cell lines. This result, along with those ones regarding changes in glyoxalases activity and expression in other human hormoneregulated cancers, such as prostate cancer, has prompted us to investigate whether also androgens, whose functional role in prostate cancer pathogenesis is well known, could modulate glyoxalases gene expression. Therefore, we treated LNCaP androgen-responsive and PC3 androgen-independent human prostate cancer cell lines with testosterone at the concentrations of 1 nM and 100 nM. After a two days treatment, glyoxalases mRNA levels as well as cell proliferation were evaluated by real-time RT-PCR analysis and [ 3 H]thymidine incorporation, respectively. Results pointed out that testosterone affects the expression of glyoxalase system genes and cell proliferation in a different manner in the two cell lines. The possibility that modulation of glyoxalase genes expression by testosterone is due to glyoxalases-mediated intracellular response mechanisms to the androgen-induced oxidative stress or to the presence of androgen response elements (ARE) in glyoxalase promoters are discussed. Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo.

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“…2) Furthermore, in many human tumors including colon, 3) pancreatic, 4) melanoma, 5) prostate, 6,7) breast 8,9) and lung, 10) and anticancer drug-resistant human leukemia cells, 11) abnormal expression and higher activity of GLO I have been reported. These observations indicate that the increased expression of GLO I is closely associated with carcinogenesis [3][4][5][6][7][8][9][10] and anticancer drug resistance.…”

mentioning

confidence: 99%

“…These observations indicate that the increased expression of GLO I is closely associated with carcinogenesis [3][4][5][6][7][8][9][10] and anticancer drug resistance. 9) So, specific inhibitors of GLO I have long been sought as possible effective anticancer drugs, which selectively kill GLO I-overexpressing and anticancer drug-resistant tumors.…”

mentioning

confidence: 99%

TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells

Takasawa

Shimada

Uchiro

et al. 2016

Biological & Pharmaceutical Bulletin

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Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosisinducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose-and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. Taken together, TLSC702 could become a unique seed compound for the generation of novel chemotherapeutic drugs targeting GLO I-dependent human tumors. Key words glyoxalase I; inhibitor; anticancer drugGlyoxalase I (GLO I) is a key enzyme in the pathways leading to glutathione (GSH)-mediated detoxification of methylglyoxal (MG), the side product of tumor-specific aerobic glycolysis (Warburg effect). 1) MG is highly reactive with DNA/ RNA and proteins and has been suggested to induce apoptosis in tumor cells.2) Furthermore, in many human tumors including colon, 3) pancreatic, 4) melanoma, 5) prostate, 6,7) breast 8,9) and lung, 10) and anticancer drug-resistant human leukemia cells, 11) abnormal expression and higher activity of GLO I have been reported. These observations indicate that the increased expression of GLO I is closely associated with carcinogenesis [3][4][5][6][7][8][9][10] and anticancer drug resistance. 9) So, specific inhibitors of GLO I have long been sought as possible effective anticancer drugs, which selectively kill GLO I-overexpressing and anticancer drug-resistant tumors. 12,13) Some GSH analogs, such as S-p-bromobenzylglutathione (BBG), 14,15) S-(N-hydroxy-N-methylcarbamoyl) glutathione, 16) and S-(N-aryl-N-hydroxycarbamoyl) glutathione derivatives, 17) have been reported as GLO I inhibitors. However, such GSH analogs are likely to be readily degraded in vivo by ubiquitously distributed γ-glutamyltranspeptidase, a GSH catabolizing enzyme. Probably, they also inhibit other GSH-dependent enzymes. Furthermore, for designing of small molecular GLO I inhibitors, it is not better to use the GSH peptide scaffold as a lead structure because of its flexibility. Therefore, the search of new types of scaffold for GLO I inhibitory small molecules is required to open a way for the development of novel anticancer drugs.Recently, we identified myricetin as a substrate transitionstate mimetic inhibitor of hGLO I.18) Based on the binding mode of myricetin to hGLO I, which was simulated ...

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Glyoxalase I Activity in Human Prostate Cancer: A Potential Marker and Importance in Chemotherapy

Abstract: Gly-I activity is indeed higher in cancerous than in noncancerous specimens, suggesting that it may play a role in prostate cancer homeostasis and survival.

Cited by 57 publications

References 9 publications

Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells

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