Catalytically Active Peptidylglycine α-Amidating Monooxygenase in the Media of Androgen-Independent Prostate Cancer Cell Lines

Peptidylglycine α-amidating monooxygenase (PAM) converts inactive terminal-glycine prohormones into their activated α-amidated forms. PAM is thought to play a role in the development of antiandrogen drug resistance in prostate cancer (CaP) through PAMactivated autocrine growth. On the basis of the previous finding that many lung cancer cell lines excrete PAM into their culture media, this study investigates PAM levels in media collected from human CaP cell line cultures. Androgen-independent DU145 and PC-3 prostate cancer cell lines exhibited readily detectable levels of PAM activity in extracts and media, whereas the androgen-dependent LNCaP cell line showed little or no activity. Because of the much larger volume of media versus cell extracts, more than 90% of the total PAM activity was located in the media for both the PC-3 and DU145 cell lines, providing a readily accessible source of CaP PAM. A simple, scalable method to obtain PAM from the culture media of androgen-independent human prostate cancer cell lines is described in this article. This approach provides a much easier means of collecting CaP-derived PAM than previously described cell fractionation procedures and should facilitate the investigations of the role and targeting of PAM in hormone-independent CaP. ( Journal of Biomolecular Screening 2008:804-809)

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Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

Medicinal Chemistry ◽

10.2174/1573406415666190613162322 ◽

2020 ◽

Vol 16 (6) ◽

pp. 735-749 ◽

Cited By ~ 1

Author(s):

Özgür Yılmaz ◽

Burak Bayer ◽

Hatice Bekçi ◽

Abdullahi I. Uba ◽

Ahmet Cumaoğlu ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Modeling ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

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DNA methylation analysis of AR gene in androgen independent prostate cancer cell lines

Journal of Men s Health ◽

10.1016/j.jomh.2009.08.067 ◽

2009 ◽

Vol 6 (3) ◽

pp. 245-245

Author(s):

B. Fialová ◽

K. Trtková ◽

Z. Kolář

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Methylation Analysis ◽

Prostate Cancer Cell Lines ◽

Dna Methylation Analysis ◽

Androgen Independent

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Thermally targeted p21 peptide enhances bortezomib cytotoxicity in androgen-independent prostate cancer cell lines

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000036 ◽

2014 ◽

Vol 25 (2) ◽

pp. 189-199 ◽

Cited By ~ 7

Author(s):

Ana-Matea Mikecin ◽

Leslie R. Walker ◽

Marija Kuna ◽

Drazen Raucher

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Androgen Independent

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Enzalutamide response in a panel of prostate cancer cell lines reveals a role for glucocorticoid receptor in enzalutamide resistant disease

Scientific Reports ◽

10.1038/s41598-020-78798-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Rebecca Smith ◽

Moqing Liu ◽

Tiera Liby ◽

Nora Bayani ◽

Elmar Bucher ◽

...

Keyword(s):

Prostate Cancer ◽

Glucocorticoid Receptor ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Response To Therapy ◽

Model Systems ◽

Prostate Cancer Cell Lines

AbstractRepresentative in vitro model systems that accurately model response to therapy and allow the identification of new targets are important for improving our treatment of prostate cancer. Here we describe molecular characterization and drug testing in a panel of 20 prostate cancer cell lines. The cell lines cluster into distinct subsets based on RNA expression, which is largely driven by functional Androgen Receptor (AR) expression. KLK3, the AR-responsive gene that encodes prostate specific antigen, shows the greatest variability in expression across the cell line panel. Other common prostate cancer associated genes such as TMPRSS2 and ERG show similar expression patterns. Copy number analysis demonstrates that many of the most commonly gained (including regions containing TERC and MYC) and lost regions (including regions containing TP53 and PTEN) that were identified in patient samples by the TCGA are mirrored in the prostate cancer cell lines. Assessment of response to the anti-androgen enzalutamide shows a distinct separation of responders and non-responders, predominantly related to status of wild-type AR. Surprisingly, several AR-null lines responded to enzalutamide. These AR-null, enzalutamide-responsive cells were characterized by high levels of expression of glucocorticoid receptor (GR) encoded by NR3C1. Treatment of these cells with the anti-GR agent mifepristone showed that they were more sensitive to this drug than enzalutamide, as were several of the enzalutamide non-responsive lines. This is consistent with several recent reports that suggest that GR expression is an alternative signaling mechanism that can bypass AR blockade. This study reinforces the utility of large cell line panels for the study of cancer and identifies several cell lines that represent ideal models to study AR-null cells that have upregulated GR to sustain growth.

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In vitro efficacy of MAGMAS inhibition in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.281 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 281-281

Author(s):

Benjamin C. Powers ◽

Bhaskar Das ◽

Boumediene Bouzahzah ◽

Peter J. Van Veldhuizen ◽

Emma Borrego-Diaz Reyes

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Gm Csf ◽

Androgen Independent

281 Background: Prostate cancer is the second most common cancer worldwide in males. The initial treatment in advanced cases is medical or surgical castration. The outlook declines when prostate cancer advances independently, despite the aforementioned castration. Within the last ten years, a handful of new agents have proven effective in this castration-resistant phase, but finding more effective, novel ways of treating advanced prostate cancer is warranted. MAGMAS (mitochondria-associated, granulocyte-macrophage colony stimulating factor (GM-CSF) signaling molecule) is a protein ubiquitously expressed in eukaryotic cells that plays a key role in embryonal development in a variety of species. Overexpression of MAGMAS has anti-apoptotic effects, as GM-CSF is a growth factor essential for survival, proliferation and differentiation of cells. MAGMAS and GM-CSF receptor levels have been shown to be overexpressed in prostate cancer, but do not correlate with pathological grade or clinical stage. The purpose of our study was to evaluate the efficacy of a MAGMAS inhibitor, synthesized by Dr Bhaskar Das, in androgen-dependent and androgen-independent prostate cancer cell lines, as well as in a normal prostate cell line as another control. Methods: The different cell lines were treated with MAGMAS inhibitor at various concentrations in vitro. For analysis, we used MTT Cell Proliferation assay at 24 and 48 hours, per manufacturer’s protocol. We tested MAGMAS inhibitor effect on apoptosis/necrosis, cell migration and microtubule destabilization as well. Results: After prostate cancer cell lines were treated with MAGMAS inhibitor in vitro, cell proliferation and migration decreased, apoptosis and necrosis were induced, and microtubules were destabilized, all showing more impressive results in the androgen-independent cells. MAGMAS inhibition did not affect cell proliferation in the normal prostate cells. Conclusions: In vitro studies show MAGMAS inhibition proves efficacious in both androgen-dependent and androgen-independent prostate cancer cell lines. This will be evaluated further in a xenograft mouse model.

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