scholarly journals Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3

2021 ◽  
Vol 22 (3) ◽  
pp. 1153
Author(s):  
Ana Paola G. Lombardi ◽  
Renan P. Cavalheiro ◽  
Catarina S. Porto ◽  
Carolina M. Vicente
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Colony Formation ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Selective Agonist ◽  
Androgen Independent

Castration-resistant prostate cancer (CRPC) is an advanced and androgen-independent form of prostate cancer. Recent studies of rapid actions mediated by estrogen in the prostate and its relationship with CRPC are emerging. We have previously shown that estrogen receptor (ER) promotes migration and invasion of the androgen-independent prostate cancer cells PC-3, but the signaling pathways involved in these events remain to be elucidated. Therefore, this study aimed to analyze the role of ERα and ERβ in the activation of SRC, and the involvement of SRC and PI3K/AKT on invasion and colony formation of the PC-3 cells. Our results showed that the activation of ERα (using ERα-selective agonist PPT) and ERβ (using ERβ-selective agonist DPN) increased phosphorylation of SRC in PC-3 cells. In the presence of the selective inhibitor for SRC-family kinases PP2, the effects of DPN and PPT on transmigration and soft agar colony formation assays were decreased. Furthermore, SRC is involved in the expression of the non-phosphorylated β-catenin. Finally, using PI3K specific inhibitor Wortmannin and AKT inhibitor MK2206, we showed that PI3K/AKT are also required for invasion and colony formation of PC-3 cells simulated by ER. This study provides novel insights into molecular mechanisms of ER in PC-3 cells by demonstrating that ER, located outside the cell nucleus, activates rapid responses molecules, including SRC and PI3K/AKT, which enhance the tumorigenic potential of prostate cancer cells, increasing cell proliferation, migration, invasion, and tumor formation.

scholarly journals Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1α

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Fei Yang ◽  
Jiarong Cai ◽  
Hailun Zhan ◽  
Jie Situ ◽  
Wenbiao Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Prostate Cancer Cells ◽  
Cell Migration And Invasion ◽  
Androgen Independent

Transient receptor potential melastatin subfamily member 7 (TRPM7) was essential in the growth and metastatic ability of prostate cancer cells. However, the effects and the relevant molecular mechanisms of TRPM7 on metastasis of prostate cancer under hypoxic atmosphere remain unclear. This study investigated the role of TRPM7 in the metastatic ability of androgen-independent prostate cancer cells under hypoxia. First, data mining was carried out to disclose the relationship between the TRPM7 gene level and the survival of prostate cancer patients. Specific siRNAs were used to knockdown target genes. Western blotting and qPCR were employed to determine protein and gene expression, respectively. The gene transcription activity was evaluated by luciferase activity assay of promoter gene. The protein interaction was determined by coimmunoprecipitation. Wound healing and transwell assays were employed to evaluated cell migration and invasion, respectively. Open access database results showed that high expression of TRPM7 was closely related to the poor survival of prostate cancer patients. Hypoxia simultaneously increased TRPM7 expression and induced HIF-1α accumulation in androgen-independent prostate cancer cells. Knockdown of TRPM7 significantly promoted HIF-1α degradation through the proteasome and inhibited EMT changes in androgen-independent prostate cancer cells under hypoxic condition. Moreover, TRPM7 knockdown increased the phosphorylation of RACK1 and strengthened the interaction between RACK1 and HIF-1α but attenuated the binding of HSP90 to HIF-1α. Whereas knockdown of RACK1 increased the binding of HSP90 to HIF-1α. Furthermore, both TRPM7 and HIF-1α knockdown significantly suppressed hypoxia-induced Annexin A1 protein expression, and suppression of HIF-1α/Annexin A1 signaling significantly inhibited hypoxia-induced cell migration and invasion of androgen-independent prostate cancer cells. Our findings demonstrate that TRPM7 knockdown promotes HIF-1α degradation via an oxygen-independent mechanism involving increased binding of RAKC1 to HIF-1α, and TRPM7-HIF-1α-Annexin A1 signaling axis plays a crucial role in the EMT, cell migration, and invasion of androgen-independent prostate cancer cells under hypoxic conditions.

scholarly journals Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle–Apoptosis and PI3K Signalling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Nurul Azwa Abd Wahab ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Morphological Observation ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Androgen Independent

Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 µM) compared to curcumin (EC50: DU 145; 34.25 ± 2.7 µM and PC-3; 27.77 ± 6.4 µM). In addition, MS13 exhibited significant anti-proliferative activity against AIPC cells compared to curcumin in a dose- and time-dependent manner. Morphological observation, increased caspase-3 activity, and reduced Bcl-2 protein levels in these cells indicated that MS13 induces apoptosis in a time- and dose-dependent. Moreover, MS13 effectively inhibited the migration of DU 145 and PC-3 cells. Our results suggest that cell cycle-apoptosis and PI3K pathways were the topmost significant pathways impacted by MS13 activity. Our findings suggest that MS13 may demonstrate the anti-cancer activity by modulating DEGs associated with the cell cycle-apoptosis and PI3K pathways, thus inhibiting cell proliferation and cell migration as well as inducing apoptosis in AIPC cells.

Ferruginol suppresses survival signaling pathways in androgen-independent human prostate cancer cells

Biochimie ◽  
2008 ◽  
Vol 90 (6) ◽  
pp. 843-854 ◽  
Author(s):  
Marcelo Bispo de Jesus ◽  
Willian Fernando Zambuzzi ◽  
Roberta Regina Ruela de Sousa ◽  
Carlos Areche ◽  
Ana Carolina Santos de Souza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Survival Signaling ◽  
Androgen Independent

Simvastatin Up-Regulates Annexin A10 That Can Inhibit the Proliferation, Migration, and Invasion in Androgen-Independent Human Prostate Cancer Cells

The Prostate ◽  
2016 ◽  
Vol 77 (4) ◽  
pp. 337-349 ◽  
Author(s):  
Yoshiyuki Miyazawa ◽  
Yoshitaka Sekine ◽  
Haruo Kato ◽  
Yosuke Furuya ◽  
Hidekazu Koike ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Annexin A10 ◽  
Androgen Independent

scholarly journals TR3 enhances AR Variant Production and Transactivation, Increasing Androgen Independency of AR Signaling in Prostate Cancer Cells

2021 ◽  
Author(s):  
Tuyen Thanh Tran ◽  
Keesook Lee
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Expression Level ◽  
Orphan Nuclear Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Androgen Independent

Abstract Background Increased expression of constitutively active androgen receptor variants (AR-Vs) is associated with the development of advanced castration-resistant prostate cancer. The pro-oncogenic function of TR3, an orphan nuclear receptor, has been reported in various cancers including prostate cancer. However, the roles of TR3 in androgen receptor (AR) expression and signaling in prostate cancer cells are poorly understood. Methods Western blotting and quantitative RT-PCR were used to evaluate AR and AR-V expression levels affected by TR3 expression level. RNA-seq analysis, coimmunoprecipitation, cross-linked RNA-immunoprecipitation, and single-strand RNA protection and pull-down assays were conducted to elucidate the molecular mechanisms by which TR3 affected AR-V production. Results Database analysis revealed that TR3 expression level is elevated in prostate tumors, and is positively correlated with that of AR. TR3 overexpression increased the production of AR splice variants in addition to general upregulation of AR expression. TR3 interacted with some spliceosomal complex components and AR precursor mRNA, altering the splice junction rates between exons. TR3 also enhanced androgen-independent AR function. Furthermore, TR3 overexpression increased cell proliferation and mobility of AR-positive prostate cancer cells and stimulated tumorigenesis of androgen-independent prostate cancer cells in mouse xenograft models. This is the first study to report that TR3 is a multifunctional regulator of AR signaling in prostate cancer cells. Conclusions TR3 alters AR expression, splicing process, and activity in prostate cancer cells, increasing the androgen independency of AR signaling. Therefore, TR3 may play a crucial role in the progression of prostate cancer to advanced castration-resistant form.

scholarly journals The Effects of Sodium Butyrate as a Histone Deacetylase Inhibitor on the Activation of Toll-Like Receptor 4 in Prostate Cancer Cells

2021 ◽  
Author(s):  
Asuman Deveci Ozkan ◽  
Gamze Guney Eskiler ◽  
Ozge Turna ◽  
Nur Kazan
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Histone Deacetylase ◽  
Sodium Butyrate ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Apoptotic Cell ◽  
Lncap Cells ◽  
Prostate Cancer Cells

Abstract I. Background: Prostate cancer is the most diagnosed cancer in men and the covalent acetylation and deacetylation of histone proteins by the histone deacetylase (HDAC) enzymes can be considered a novel therapeutic target in PCa cells. Sodium butyrate (NaBu) is one of the most studied HDAC inhibitor (HDACi) which is a promising potential anticancer drug. Toll-like receptors (TLRs) are expressed on prostate cells and TLR4 expression is increased in prostate cancer cells and HDACi alter TLR-inducible gene expressions. Therefore, we aimed to evaluate the effects of NaBu on TLR4 mediating signaling pathways in two different PCa cells (DU-145 and LNCaP) for the first time.II. Methods and Results: The cytotoxicity of NaBu in PCa cells was determined by WST-1 assay. Apoptotic effects of NaBu were analyzed by Annexin V and AO/PI assays. Subcellular localization of TLR4, IRF3 and NF-κB proteins was evaluated by IF assay. Our results showed that NaBu significantly inhibited the viability of PCa cells and increased the percentage of apoptotic cells (p<0.01). However, DU-145 cells were more sensitive to NaBu than LNCaP cells. Furthermore, NaBu can induce the cytoplasmic TLR4 and IRF3 expression in particularly DU-145 cells without affecting nuclear translocation of NF-kB in PCa cells.III. Conclusions: NaBu induces apoptotic cell death and regulated the TLR4/IRF3 signaling pathways in DU-145 cells but not in LNCaP cells. Therefore, PCa cells differentially responded to NaBu treatment due to probably AR status. Therefore, further investigations should be performed to assess the molecular mechanisms underlying cell response to NaBu-induced TLR-mediated signaling pathways in vitro and in vivo.

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