EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer

Kashiwagi, Eiji; Shiota, Masaki; Yokomizo, Akira; Inokuchi, Junichi; Uchiumi, Takeshi; Naito, Seiji

doi:10.1038/pcan.2013.53

Cited by 23 publications

(22 citation statements)

References 42 publications

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“…Knock-down of the CACNA1C -encoded Ca V 1.2 channel did not show any effects [ 88 ]. Additional evidence for a pathologic Ca V 1.3 up-regulation is based on pharmacologic studies with the cyclooxygenase-2 inhibitor, celecoxib, which exerts chemopreventive effects against multiple cancers, including prostate cancer [ 89 ]. These effects appear to be mediated at least in part by down-regulation of androgen receptors [ 89 ].…”

Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

“…Additional evidence for a pathologic Ca V 1.3 up-regulation is based on pharmacologic studies with the cyclooxygenase-2 inhibitor, celecoxib, which exerts chemopreventive effects against multiple cancers, including prostate cancer [ 89 ]. These effects appear to be mediated at least in part by down-regulation of androgen receptors [ 89 ]. However, it is tempting to speculate that down-regulation is the result of celecoxib’s inhibitory effects on Ca V 1 channel-mediated L-type Ca ++ currents [ 89 , 90 ].…”

Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

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Voltage-Gated Ion Channels in Cancer Cell Proliferation

Rao¹,

Perez-Neut²,

Kaja³

et al. 2015

Cancers

175

160

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Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting that VGIC play a major role in cancer cell biology, in this review we discuss the role of distinct VGIC in cancer cell proliferation and possible therapeutic potential of VIGC pharmacological manipulation.

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Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

Voltage-Gated Ion Channels in Cancer Cell Proliferation

Rao¹,

Perez-Neut²,

Kaja³

et al. 2015

Cancers

175

160

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“…Aspirin is one of the most commonly used NSAIDs and has shown activity in a variety of cancers, including prostate cancer (16)(17)(18). Although results from several epidemiological studies for the association of aspirin use and prostate cancer were controversial (19)(20)(21), a recent meta-analysis of prospective and case-control cohort studies including over 100,000 prostate cancer cases worldwide found that aspirin was associated with a reduced risk of total prostate cancer and prostate cancer-specific mortality (22).…”

Section: Introductionmentioning

confidence: 99%

Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Huang

Farischon

et al. 2017

Oncology Reports

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Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in prostate cancer cells were determined by the trypan blue exclusion and propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in Matrigel. After 4-6 weeks, mice with PC-3 tumors received i.p. injections of vehicle, atorvastatin (5 mg/kg), aspirin (80 mg/kg), or atorvastatin (5 mg/kg) + aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of atorvastatin and aspirin had more potent effects on growth inhibition and apoptosis stimulation in prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of atorvastatin and aspirin on inhibiting the growth of prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of atorvastatin and aspirin in patients with prostate cancer.

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“…35 However, the concentration of the agents was observed to be critical in balancing anti-inflammatory activity and further carcinogenic alterations such as protein stability of AR, as well as NKX3.1 and Akt activation, as found in our study. 36 We suggest that these results are significant for the selection of the best therapy among many anti-inflammatory therapy alternatives for prostatic inflammation because our findings show the secondary effects of commonly used NSAIDs on carcinogenesis-related AR signaling abrogation and Akt activation in prostate cells.…”

Section: Discussionmentioning

confidence: 81%

Use of Non-steroidal Anti-inflammatory Drugs for Chemoprevention of Inflammation-induced Prostate Cancer

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2017

tjps

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Amaç: Kronik enflamasyonun kanser gelişiminin önemli nedenlerinden biri olduğu ve epidemiyolojik verilere göre kanser olgularının %25'inin kronik inflamasyona bağlı olarak geliştiği bilinmektedir. Kronik inflamasyon, hücre proliferasyonu, apoptoz, anjiyogenez gibi mekanizmalarda bozukluklara yol açarak tümörleşmeyi tetiklemektedir. Bu nedenle kanseri önleyici ilaç geliştirme çalışmalarında, inflamasyon ile tetiklenen mekanizmaların inhibisyonununda etkin bir terapötik strateji olduğu düşünülmektedir. Klinik çalışmalarda da, birçok kanser tipinde anti-inflamatuvar ilaçların kanser insidansını azaltıcı etkisi belirlenmiş ve prostat kanserinde de düzenli aspirin veya non-streoidal anti-inflamatuvar ilaç (NSAID) kullananların prostat kanserine yakalanma riskinin yaklaşık %15-20 azaldığı saptanmıştır. Gereç ve Yöntemler: Bu çalışma kapsamında, klinik kullanımdaki NSAID'lerden indometazin, sulindak, ibuprofen, naproksen, selekoksib ve nimesulidin inflamasyona bağlı prostat kanserleşmesinde rol oynayan moleküler mekanizmalardan bazıları üzerindeki etkileri araştırılmıştır. Tümörijenik mekanizmaları aktifleştiren nükleer faktör kappa B sinyal yolağı üzerindeki inhibisyon etkileri ve prostat hücrelerinin proliferasyonunu düzenleyen androjen reseptörü sinyal yolağı üzerindeki etkileri araştırılmıştır. Ayrıca inflamatuvar mikroçevrede etkinleşerek tümörleşmeye neden olan protein kinaz B (Akt) aktivitesindeki değişim de incelenmiştir. Bulgular: Elde edilen sonuçlar, anti-inflamatuvar ajanların, androjen reseptörü ve tümör baskılayıcı NKX3.1'in protein seviyelerinde konsantrasyona bağlı bir değişime neden olduğu, ayrıca tümörleşmeyi tetikleyen Akt (S473) düzeyinde de beklenmedik bir aktivasyonu tetikleyebildiğini göstermiştir. Sonuç: Anti-inflamatuvar ajanların, prostat inflamasyonu ile tetiklenen kanserleşme sürecini önleme amacıyla kullanımlarında yalnızca inflamatuvar yolakların değil prostat kanserleşmesine özgün mekanizmaların da dikkate alınması gereği ortaya konmuştur. Anahtar kelimeler: NSAID, prostat kanseri, inflamasyon, androjen reseptörü, NKX3.1 Objectives: Chronic inflammation has been known as one of the major causes of cancer progression and 25% of cancer cases initiate due to chronic inflammation according to epidemiologic data. It has been determined that chronic inflammation induces carcinogenesis through the abrogation of cell proliferation, apoptosis, and angiogenesis mechanisms. Therefore, it is believed that inhibition of inflammation-induced carcinogenic mechanisms is an efficient therapeutic strategy in drug development studies of cancer chemoprevention. It has also been observed that use of anti-inflammatory drugs reduces the incidence of cancer, and the risk of developing prostate cancer decreases 15-20% with regular use of aspirin and non-steroidal anti-inflammatory drugs (NSAID). Materials and Methods:In this study, we investigated the effects of some clinically used NSAIDs on cellular mechanisms that play a role in inflammation-induced prostate carcinogenesis. Inhibition activities on the...

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EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer

Abstract: Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.

Cited by 23 publications

References 42 publications

Voltage-Gated Ion Channels in Cancer Cell Proliferation

Voltage-Gated Ion Channels in Cancer Cell Proliferation

Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells

Use of Non-steroidal Anti-inflammatory Drugs for Chemoprevention of Inflammation-induced Prostate Cancer

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