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Oxidative stress in prostate hyperplasia and carcinogenesis

View Article: PubMed Central - PubMed

ABSTRACT

Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment.

No MeSH data available.


Related in: MedlinePlus

Gene Involved in the signaling pathways which contribute to the development and progression (including invasion, metastasis, and relapse) of PCa: The genes that maintain hemostasis receive attack from pro-oxidative stress genes and genes that are involved in metastasis. DNA damage leads to suppression of antioxidant pro-gene and this gives way to the over-expression of cancer promoting genes
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Fig6: Gene Involved in the signaling pathways which contribute to the development and progression (including invasion, metastasis, and relapse) of PCa: The genes that maintain hemostasis receive attack from pro-oxidative stress genes and genes that are involved in metastasis. DNA damage leads to suppression of antioxidant pro-gene and this gives way to the over-expression of cancer promoting genes

Mentions: PCa tumorigenesis involves a combo of genes such as the antioxidant enzyme heme oxygenase 1 (HMOX1/HO-1) which is responsible for the maintenance of the cellular homeostasis (See Fig. 6). HMOX1/HO-1 plays a critical role in oxidative stress mechanism and in the regulation of PCa development and progression. The transcription factor Nrf2 and BRCA1 protein synergistically activate HO-1 promoter activity forming BRCA1-Nrf2/HO-1 which function in the maintenance of the cellular homeostasis in PCa. They exert both oxidative and genotoxic stress on HO-1 transcriptional activity [135]. ROS increase the expression and activity of the chemokine receptor, cysteine (C)-X-C Receptor 4 (CXCR4), which enhances metastatic functions in prostate cancer cells. Also, CXCR4 and its ligand, SDF-1α, promote ROS accumulation contributed by the NADPH oxidase (NOX) family of enzymes. NOX2 expression is associated with PCa. CXCR4/SDF-1α-mediated ROS production through NOX2 enzymes may be an emerging concept by which chemokine signaling progresses tumorigenesis [136]. Glyoxalase 1 (GLO1) is a glutathione-dependent enzyme that acts as a scavenging enzyme. It participates in ROS mechanism and is involved in the occurrence and progression of human malignancies. Polymorphism in Glyoxalase I A111E may influence its enzymatic activity. GLO1 could be important in PCa progression and may be a good marker for risk assessment and prognosis in PCa patients [137]. Another gene, prostate-associated gene 4 (PAGE4) encodes a protein which protects cells against stress by elevating p21 and suppressing ROS production. PAGE4 is a cancer/testis antigen (CTA) that is up-regulated in PCa and seen in symptomatic patients. However, PAGE4 appears to protect cells from transforming to PCa by its stress-protective and anti-apoptotic activities [138]. The role of OS and diet in PCa mechanism was observed with the prostate-specific ablation of PPARγ in mice. This action resulted in tumorigenesis and active autophagy. Placing the mice on high-fat diet (HFD) caused downregulation of PPARγ-regulated genes and decreased prostate differentiation. This suggests that systemic metabolic stress occurs in glucose and fatty acid metabolism in benign and PCa [67].Fig. 6


Oxidative stress in prostate hyperplasia and carcinogenesis
Gene Involved in the signaling pathways which contribute to the development and progression (including invasion, metastasis, and relapse) of PCa: The genes that maintain hemostasis receive attack from pro-oxidative stress genes and genes that are involved in metastasis. DNA damage leads to suppression of antioxidant pro-gene and this gives way to the over-expression of cancer promoting genes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5017015&req=5

Fig6: Gene Involved in the signaling pathways which contribute to the development and progression (including invasion, metastasis, and relapse) of PCa: The genes that maintain hemostasis receive attack from pro-oxidative stress genes and genes that are involved in metastasis. DNA damage leads to suppression of antioxidant pro-gene and this gives way to the over-expression of cancer promoting genes
Mentions: PCa tumorigenesis involves a combo of genes such as the antioxidant enzyme heme oxygenase 1 (HMOX1/HO-1) which is responsible for the maintenance of the cellular homeostasis (See Fig. 6). HMOX1/HO-1 plays a critical role in oxidative stress mechanism and in the regulation of PCa development and progression. The transcription factor Nrf2 and BRCA1 protein synergistically activate HO-1 promoter activity forming BRCA1-Nrf2/HO-1 which function in the maintenance of the cellular homeostasis in PCa. They exert both oxidative and genotoxic stress on HO-1 transcriptional activity [135]. ROS increase the expression and activity of the chemokine receptor, cysteine (C)-X-C Receptor 4 (CXCR4), which enhances metastatic functions in prostate cancer cells. Also, CXCR4 and its ligand, SDF-1α, promote ROS accumulation contributed by the NADPH oxidase (NOX) family of enzymes. NOX2 expression is associated with PCa. CXCR4/SDF-1α-mediated ROS production through NOX2 enzymes may be an emerging concept by which chemokine signaling progresses tumorigenesis [136]. Glyoxalase 1 (GLO1) is a glutathione-dependent enzyme that acts as a scavenging enzyme. It participates in ROS mechanism and is involved in the occurrence and progression of human malignancies. Polymorphism in Glyoxalase I A111E may influence its enzymatic activity. GLO1 could be important in PCa progression and may be a good marker for risk assessment and prognosis in PCa patients [137]. Another gene, prostate-associated gene 4 (PAGE4) encodes a protein which protects cells against stress by elevating p21 and suppressing ROS production. PAGE4 is a cancer/testis antigen (CTA) that is up-regulated in PCa and seen in symptomatic patients. However, PAGE4 appears to protect cells from transforming to PCa by its stress-protective and anti-apoptotic activities [138]. The role of OS and diet in PCa mechanism was observed with the prostate-specific ablation of PPARγ in mice. This action resulted in tumorigenesis and active autophagy. Placing the mice on high-fat diet (HFD) caused downregulation of PPARγ-regulated genes and decreased prostate differentiation. This suggests that systemic metabolic stress occurs in glucose and fatty acid metabolism in benign and PCa [67].Fig. 6

View Article: PubMed Central - PubMed

ABSTRACT

Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment.

No MeSH data available.


Related in: MedlinePlus