scholarly journals Small-molecule screening of PC3 prostate cancer cells identifies tilorone dihydrochloride to selectively inhibit cell growth based on cyclin-dependent kinase 5 expression

2014 ◽  
Vol 32 (1) ◽  
pp. 419-424 ◽  
Author(s):  
MICHEL D. WISSING ◽  
TIKVA DADON ◽  
EUNICE KIM ◽  
KLAUS B. PIONTEK ◽  
JOONG S. SHIM ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Small Molecule ◽  
Cyclin Dependent Kinase ◽  
Prostate Cancer Cells ◽  
Small Molecule Screening ◽  
Inhibit Cell Growth ◽  
Cyclin Dependent Kinase 5

scholarly journals Cyclin-Dependent Kinase 5 Activity Controls Cell Motility and Metastatic Potential of Prostate Cancer Cells

2006 ◽  
Vol 66 (15) ◽  
pp. 7509-7515 ◽  
Author(s):  
Christopher J. Strock ◽  
Jong-In Park ◽  
Eric K. Nakakura ◽  
G. Steven Bova ◽  
John T. Isaacs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Metastatic Potential ◽  
Cyclin Dependent Kinase ◽  
Prostate Cancer Cells ◽  
Cyclin Dependent Kinase 5

scholarly journals Silibinin synergizes with mitoxantrone to inhibit cell growth and induce apoptosis in human prostate cancer cells

2007 ◽  
Vol 120 (9) ◽  
pp. 2028-2033 ◽  
Author(s):  
Thomas W. Flaig ◽  
Lih-Jen Su ◽  
Gail Harrison ◽  
Rajesh Agarwal ◽  
Leonard Michael Glodé
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Inhibit Cell Growth

Macrocyclic Polyamines Deplete Cellular ATP Levels and Inhibit Cell Growth in Human Prostate Cancer Cells

2004 ◽  
Vol 47 (4) ◽  
pp. 1051-1059 ◽  
Author(s):  
Benjamin Frydman ◽  
Subhra Bhattacharya ◽  
Aparajita Sarkar ◽  
Konstantin Drandarov ◽  
Sergiy Chesnov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Atp Levels ◽  
Macrocyclic Polyamines ◽  
Inhibit Cell Growth

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells

The Prostate ◽  
2017 ◽  
Vol 77 (9) ◽  
pp. 955-961 ◽  
Author(s):  
Daisuke Nakata ◽  
Ryokichi Koyama ◽  
Kazuhide Nakayama ◽  
Satoshi Kitazawa ◽  
Tatsuya Watanabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Prostate Cancer Cells ◽  
Inhibit Cell Growth

Cyclin-dependent kinase 5 modulates STAT3 and androgen receptor activation through phosphorylation of Ser727 on STAT3 in prostate cancer cells

2013 ◽  
Vol 305 (8) ◽  
pp. E975-E986 ◽  
Author(s):  
Fu-Ning Hsu ◽  
Mei-Chih Chen ◽  
Kuan-Chia Lin ◽  
Yu-Ting Peng ◽  
Pei-Chi Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Receptor Activation ◽  
Cyclin Dependent Kinase ◽  
Prostate Cancer Cells ◽  
Cell Proliferation Control ◽  
Cyclin Dependent Kinase 5

Cyclin-dependent kinase 5 (Cdk5) is known to regulate prostate cancer metastasis. Our previous results indicated that Cdk5 activates androgen receptor (AR) and supports prostate cancer growth. We also found that STAT3 is a target of Cdk5 in promoting thyroid cancer cell growth, whereas STAT3 may play a role as a regulator to AR activation under cytokine control. In this study, we investigated the regulation of Cdk5 and its activator p35 on STAT3/AR signaling in prostate cancer cells. Our results show that Cdk5 biochemically interacts with STAT3 and that this interaction depends on Cdk5 activation in prostate cancer cells. The phosphorylation of STAT3 at Ser727 (p-Ser727-STAT3) is regulated by Cdk5 in cells and xenograft tumors. The mutant of STAT3 S727A reduces its interaction with Cdk5. We further show that the nuclear distribution of p-Ser727-STAT3 and the expression of STAT3-regulated genes ( junB, c-fos, c-myc, and survivin) are regulated by Cdk5 activation. STAT3 mutant does not further decrease cell proliferation upon Cdk5 inhibition, which implies that the role of STAT3 regulated by Cdk5 correlates to cell proliferation control. Interestingly, Cdk5 may regulate the interaction between STAT3 and AR through phosphorylation of Ser727-STAT3 and therefore upregulate AR protein stability and transactivation. Correspondingly, clinical evidence shows that the level of p-Ser727-STAT3 is significantly correlated with Gleason score and the levels of upstream regulators (Cdk5 and p35) as well as downstream protein (AR). In conclusion, this study demonstrates that Cdk5 regulates STAT3 activation through Ser727 phosphorylation and further promotes AR activation by protein-protein interaction in prostate cancer cells.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

scholarly journals Recruitment of β-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells

2004 ◽  
Vol 18 (10) ◽  
pp. 2388-2401 ◽  
Author(s):  
David Masiello ◽  
Shao-Yong Chen ◽  
Youyuan Xu ◽  
Manon C. Verhoeven ◽  
Eunis Choi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nuclear Receptor ◽  
Specific Antigen ◽  
Prostate Cancer Cells ◽  
Prostate Cell ◽  
Nuclear Receptor Corepressor ◽  
Prostate Cancers

Abstract Prostate cancers respond to treatments that suppress androgen receptor (AR) function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR antagonists in clinical use. As CPA has substantial agonist activity, it was examined to identify AR coactivator/corepressor interactions that may mediate androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal interactions or recruit β-catenin, indicating a nonagonist conformation. Nonetheless, CPA did not enhance AR interaction with nuclear receptor corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated AR-nuclear receptor corepressor binding. The role of coactivators was further assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by β-catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and not β-catenin. In contrast, β-catenin coactivated a bicalutamide-responsive mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further implicating β-catenin recruitment in AR-stimulated growth. Androgen-stimulated prostate-specific antigen gene expression in LNCaP cells could be modulated by β-catenin, and endogenous c-myc expression was repressed by dihydrotestosterone, but not CPA. These results indicate that interactions between AR and β-catenin contribute to prostate cell growth in vivo, although specific growth promoting genes positively regulated by AR recruitment of β-catenin remain to be identified.

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