Expression of 11β-hydroxysteroid dehydrogenase types 1 and 2 in colorectal cancer

Žbánková, Šárka; Bryndová, Jana; Kment, Milan; Pácha, Jiřı́

doi:10.1016/j.canlet.2003.12.019

Cited by 24 publications

(14 citation statements)

References 22 publications

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“…From this dataset a number of the genes (CCDC8, HOXD13, SPON1, PTGS1, HSD11B1, ZFHX1B, SYNPO, UNC5B, S100A4) observed to be overexpressed in normal TZ tissues, which were hitherto identified to be downregulated in prostate cancer cells and CaP tissues, were noted. [24][25][26][27] No genes preferentially expressed in normal PZ tissues were noted on the exon array (unpublished data). However, SFRP4 was actually downregulated in the exon array but the literature reports that this is overexpressed in CaP.…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Noël

Ragavan

James

et al. 2007

Prostate Cancer Prostatic Dis

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Section: Discussionmentioning

confidence: 99%

Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Noël

Ragavan

James

et al. 2007

Prostate Cancer Prostatic Dis

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“…To the best of our knowledge, this is the first report on in silico prediction of the toxic effects of triterpenoids on tumor cells by 11␤HSD2 inhibition. 11␤HSD2 has been reported to be associated with various cancers and identified as a possible target for the prevention and therapy of cancer (12)(13)(14)(15)(16). In recent years, molecular modeling has gained much importance in the field of drug discovery and development (47)(48)(49), and further in silico studies of 11␤HSD2 and its interactions with possible ligands are expected for the successful development of antitumor drugs targeting 11␤HSD2.…”

Section: Discussionmentioning

confidence: 99%

“…4, B and D). 11␤HSD2 is overexpressed in various tumor cells (12)(13)(14)(15)(16), including the tumorigenic r/m HM-SFME-1 cells (Fig. 7, A and B).…”

Section: Discussionmentioning

confidence: 99%

“…11␤-Hydroxysteroid dehydrogenase type 2 (11␤HSD2) requires NAD ϩ , shows dehydrogenase activity for endogenous glucocorticoids such as corticosterone (CORT; 9 -11), and has been reported to be associated most notably with pituitary adenomas in the CNS (12), but also with colonic adenomas (13) and breast (14,15) and colorectal (16) cancers. The underlying explanation for the aberrant 11␤HSD2 expression is uncertain, but it has been postulated to control glucocorticoid regulation of cellular proliferation (17).…”

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confidence: 99%

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Ligand-receptor Interaction between Triterpenoids and the 11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) Enzyme Predicts Their Toxic Effects against Tumorigenic r/m HM-SFME-1 Cells

Yamaguchi

Tang

Noshita

et al. 2011

Journal of Biological Chemistry

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The present study deals with in silico prediction and in vitro evaluation of the selective cytotoxic effects of triterpenoids on tumorigenic human c-Ha-ras and mouse c-myc cotransfected highly metastatic serum-free mouse embryo-1 (r/m HM-SFME-1) cells. Ligand fitting of five different triterpenoids to 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2) was analyzed with a molecular modeling method, and glycyrrhetinic acid (GA) was the best-fitted triterpenoid to the ligand binding site in 11␤HSD2. Analysis of antiproliferative effects revealed that GA, oleanolic acid, and ursolic acid had selective toxicity against the tumor cells and that GA was the most potent triterpenoid in its selectivity. The toxic activity of the tested triterpenoids against the tumor cells showed good correlations with the partition coefficient (logP) and polar surface area values. Time-lapse microscopy, fluorescence staining, and confocal laser scanning microscopic observation revealed that GA induced morphologic changes typical of apoptosis such as cell shrinkage and blebbing and also disrupted the cytoskeletal proteins. Furthermore, GA exhibited a strong inhibitory effect on 11␤HSD2 activity in the tumor cells. Our current results suggest that analysis of the ligand-receptor interaction between triterpenoids and 11␤HSD2 can be utilized to predict their antitumor effects and that GA can be used as a possible chemopreventive and therapeutic antitumor agent. To the best of our knowledge, this is the first report on in silico prediction of the toxic effects of triterpenoids on tumor cells by 11␤HSD2 inhibition.Triterpenoids, which are biosynthesized in plants by cyclization of squalene, are widely distributed throughout the vegetable kingdom, utilized in many food products and the major components of medicinal plants used in Asian countries (1). There is a growing interest in elucidating the biological and pharmacological roles of triterpenoids in analgesic, anti-inflammatory, anti-tumor, hepatoprotective, and immunomodulatory effects (1), and we have been focusing our attention on certain triterpenoids as multifunctional agents for the prevention and treatment of cancer. Recently, we found that ursolic acid (UA) 2 from apples was selectively toxic to tumorigenic human c-Ha-ras and mouse c-myc cotransfected highly metastatic serum-free mouse embryo-1 (r/m HM-SFME-1) cells (2). We further found that glycyrrhetinic acid (GA), a licorice component, was not only selectively toxic to the tumor cells but also more potent than some clinically available antitumor agents in its selectivity (3). SFME cells, which were established by Loo et al. (4), were originally derived from a 16-day-old whole Balb/c mouse embryo and are maintained in a serum-free culture medium. These cells do not undergo growth crisis, maintain their diploid karyotype for extended passages, and are non-tumorigenic in vivo. Consequently, they are non-transformed, behave as primary cultures, have a finite lifespan, and display the characteristics of the CNS progenitor cells (5, 6)....

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“…In intestinal tumors, 11ßHSD2 is expressed in epithelial and stromal cells [37][38][39]. Interestingly, the incidence of intestinal tumors is higher in the colon than in the small intestine.…”

Section: Cyclooxygenase-2 and Glucocorticoids In Tumorigenesismentioning

confidence: 99%

11β-hydroxysteroid dehydrogenase type II: a Potential target for prevention of colonic tumorigenesis

Wang¹,

Harris²,

Zhang³

2016

Integr Cancer Sci Therap

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Cancer is the second most common cause of death in the world, and primary prevention remains the best approach to reducing overall morbidity and mortality. There is a molecular link between cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production and colonic tumorigenesis. Selective COX-2 inhibitors as well as non-steroidal anti-inflammatory drugs (NSAIDs) reduce the number and sizes of colonic adenomas; however, increased cardiovascular risks of selective COX-2 inhibitors and increased gastrointestinal side-effects of NSAIDs limit their use. Glucocorticoids induce cancer cell apoptosis and are endogenous, potent COX-2 inhibitors. In tissues, glucocorticoid actions are down-regulated by type 2 11ß-hydroxysteroid dehydrogenase (11ßHSD2), and inhibition of 11ßHSD2 activity will elevate intracellular active glucocorticoids to levels that effectively suppress COX-2 expression. Both COX-2 and 11ßHSD2 increase in Apc+/min mouse intestinal adenomas and human colonic adenomas, and either pharmacologic or genetic 11βHSD2 inhibition leads to decreases in COX-2-mediated PGE2 production in tumors and prevents adenoma formation, tumor growth, and metastasis. 11ßHSD2 inhibition may represent a novel approach for CRC chemoprevention by increasing tumor cell intracellular glucocorticoid activity, which in turn inhibits tumor growth by suppressing the COX-2-derived PGE2 pathway, as well as other pathways, without potential side-effects relating to chronic application of COX-2 inhibitors, NSAIDs and glucocorticoids.

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Expression of 11β-hydroxysteroid dehydrogenase types 1 and 2 in colorectal cancer

Cited by 24 publications

References 22 publications

Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Ligand-receptor Interaction between Triterpenoids and the 11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) Enzyme Predicts Their Toxic Effects against Tumorigenic r/m HM-SFME-1 Cells

11β-hydroxysteroid dehydrogenase type II: a Potential target for prevention of colonic tumorigenesis

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