Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development

Ishiguro, Hitoshi; Nakaigawa, Noboru; Miyoshi, Yasuhide; Fujinami, Kiyoshi; Kubota, Yoshinobu; Uemura, Hiroji

doi:10.1002/pros.20219

Cited by 188 publications

(177 citation statements)

References 20 publications

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“…Over-expression of HMGB1 is reported in prostate cancer cells (50,51) and depletion of HMGB1 expression induces apoptosis in prostate cancer cells (52). HMGB1 is a potent attractant for inflammatory cells including neutrophils, monocytes and macrophages as well as inducer of pro-inflammatory cytokines such as TNF-α, IL-1α, IL-1β, IL-6 and IL-8 production (53,54).…”

Section: Discussionmentioning

confidence: 99%

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Munirathinam

2011

Int J Oncol

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Abstract. Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also downregulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Munirathinam

2011

Int J Oncol

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“…2,34 AGEs cell surface receptor (RAGE) is an immunoglobulin superfamily member, whose overexpression has been recently associated with prostate cancer (PCa) development either in vivo or in vitro. 35 Therefore, the overexpression of RAGE on LNCaP cells may potentiate the antiproliferative effect of free MG, via MG/AGE-RAGE complexes, thus contributing to the observed reduction in cell proliferation in the presence of GI mRNA levels likely non-sufficient to produce enough protein. Similarly, it is likely that the high expression levels of GII gene, occurring simultaneously with the high GI gene expression, may be the consequence of a major cell request of the corresponding GII enzyme essential to lower the …”

Section: Discussionmentioning

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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“…Regarding tumorigenesis, RAGE and its ligands are commonly overexpressed in most types of solid tumors [18,[38][39][40][41][42][43][44][45][46][47][48]. For example, both amphoterin and RAGE are overproduced in inflammatory states, as well as in many malignant tumors with high metastatic capacity [42][43][44][45][46][47][48].…”

Section: Introductionmentioning

confidence: 99%

“…For example, both amphoterin and RAGE are overproduced in inflammatory states, as well as in many malignant tumors with high metastatic capacity [42][43][44][45][46][47][48]. However, a recent study showed that increased plasma AGE levels are associated with a protective effect over non-small cell lung cancer (NSCLC) tumor progression, presenting a simple predictor of patients' outcome after curative surgery [49].…”

Section: Introductionmentioning

confidence: 99%

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Marinakis

Bagkos

Piperi

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.

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Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development

Abstract: The AGE-RAGE interaction is important in prostate cancer development, and inhibition of this interaction has potential as a new molecular target for cancer therapy or prevention.

Cited by 188 publications

References 20 publications

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

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

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

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