Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: Preventive effects of celecoxib

Narayanan, Narayanan K.; Nargi, Dominick; Horton, Lori; Reddy, Bandaru S.; Bosland, Maarten C.; Narayanan, Bhagavathi A.

doi:10.1002/pros.20862

Cited by 30 publications

(25 citation statements)

References 36 publications

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“…Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce inflammation and prevent PCa development in a rat model of prostate carcinogenesis (Narayanan et al 2009). The use of NSAIDs such as aspirin has also been shown to lower serum prostate-specific antigen (PSA) levels in men with latent PCa (Singer et al 2008, Fowke et al 2009).…”

Section: Inflammation and Pcamentioning

confidence: 99%

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Krishnan¹,

Feldman²

2010

Endocrine-Related Cancer

127

118

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Calcitriol, the hormonally active form of vitamin D, exerts multiple anti-proliferative and pro-differentiating actions including cell cycle arrest and induction of apoptosis in many malignant cells, and the hormone is currently being evaluated in clinical trials as an anti-cancer agent. Recent research reveals that calcitriol also exhibits multiple anti-inflammatory effects. First, calcitriol inhibits the synthesis and biological actions of pro-inflammatory prostaglandins (PGs) by three mechanisms: i) suppression of the expression of cyclooxygenase-2, the enzyme that synthesizes PGs; ii) up-regulation of the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme that inactivates PGs; and iii) down-regulation of the expression of PG receptors that are essential for PG signaling. The combination of calcitriol and nonsteroidal anti-inflammatory drugs results in a synergistic inhibition of the growth of prostate cancer (PCa) cells and offers a potential therapeutic strategy for PCa. Second, calcitriol increases the expression of mitogenactivated protein kinase phosphatase 5 in prostate cells resulting in the subsequent inhibition of p38 stress kinase signaling and the attenuation of the production of pro-inflammatory cytokines. Third, calcitriol also exerts anti-inflammatory activity in PCa through the inhibition of nuclear factor-kB signaling that results in potent anti-inflammatory and anti-angiogenic effects. Other important direct effects of calcitriol as well as the consequences of its anti-inflammatory effects include the inhibition of tumor angiogenesis, invasion, and metastasis. We hypothesize that these anti-inflammatory actions, in addition to the other known anti-cancer effects of calcitriol, play an important role in its potential use as a therapeutic agent for PCa. Calcitriol or its analogs may have utility as chemopreventive agents and should be evaluated in clinical trials in PCa patients with early or precancerous disease.

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Section: Inflammation and Pcamentioning

confidence: 99%

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Krishnan¹,

Feldman²

2010

Endocrine-Related Cancer

127

118

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“…5,6 Similar to obese men, obese mice fed a high fat diet also results in increased adiposity, circulating growth factors and inflammation when compared with control mice and may contribute to prostate cancer progression. [7][8][9][10] Studies suggest that cancer cells undergo an epithelialmesenchymal-transition (EMT) program at the initiation of invasion, which is a critical process for metastasis. 11,12 Hallmarks of EMT include loss or decreased protein expression of e-cadherin, increased vimentin and deregulation of b-catenin.…”

Section: Introductionmentioning

confidence: 99%

Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells

Price

Cavazos

Angel

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND: Obesity is associated with larger tumors, shorter time to PSA failure, and higher Gleason scores. However, the mechanism(s) by which obesity promotes aggressive prostate cancer remains unknown. We hypothesize that circulating factors related to obesity promote prostate cancer progression by modulating components of the metastatic cascade.METHODS: Male C57BL/6 mice (6 weeks) were fed an ad libitum diet-induced obesity (60% fat) or control diet (10% fat) for 12 weeks. Serum was collected, metabolic and inflammatory proteins were measured by an antibody array. Sera were used to measure, in vitro, characteristics of a metastatic phenotype. RESULTS:Comparable to obese men, obese sera contained higher levels or leptin, vascular endothelial growth factor, PAI-1, interleukin-6 (IL-6) and lower levels of testosterone. In prostate cells, serum was used to assess: proliferation, invasion, migration, epithelial-mesenchymal-transition (EMT) and matrix metalloproteinase (MMP) activity. LNCaP and PacMetUT1 cells exposed to obese sera increased proliferation, whereas PrEC and DU145 were unaffected. LNCaP, PacMetUT1 and DU145 cancer cells exposed to obese sera resulted in increased invasion, migration and MMP-9 activity. Prostate cancer cells exposed to obese sera showed increased vimentin, dispersion of e-cadherin and b-catenin from the plasma membrane. CONCLUSION:We report, prostate cancer cells exposed to sera from obese mice increases proliferation, invasion, migration, MMP activity and induces changes in proteins critical for EMT.

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“…20 Furthermore, a key role for COX-2 in carcinogenesis has been given by the positive effect of its downregulation on tumors incidence both in clinical and experimental studies for distinct types of tumors, including the bladder cancer. 17,18,[21][22][23]26 A chemopreventive role for COX-2 inhibition in bladder cancer was previously reported in animal models, [26][27][28] but the mechanisms by which these compounds are able to act on carcinogenesis remain to be elucidated. In our study, the COX-2 inhibitor (CEL) has promoted a remarkable chemopreventive effect on bladder cancer development.…”

Section: Resultsmentioning

confidence: 99%

“…20 According to several studies, the modulation of mice COX-2 levels and/or activity, by genetic deletion or chemical inhibition, has decreased tumors development. Therefore, the use of selective COX-2 inhibitors (Coxibs) for chemoprevention was already tested in other types of cancer, [21][22][23] but its efficacy in bladder cancer has been poorly investigated.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

Parada

Sereno²,

Reis³

et al. 2009

Cancer Biology & Therapy

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Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: Preventive effects of celecoxib

Abstract: Carcinogen plus testosterone induced prostate carcinogenesis showing activation of macrophage, iNOS and NF-kappaBp65 could be prevented by celecoxib or related anti-inflammatory agents.

Cited by 30 publications

References 36 publications

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment

Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

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