scholarly journals Unexpected paracrine action of prostate cancer cells harboring a new class of androgen receptor mutation—A new paradigm for cooperation among prostate tumor cells

2007 ◽  
Vol 121 (6) ◽  
pp. 1238-1244 ◽  
Author(s):  
Gaëlle Lapouge ◽  
Eva Erdmann ◽  
Gemma Marcias ◽  
Monika Jagla ◽  
Audrey Monge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Prostate Tumor ◽  
Prostate Cancer Cells ◽  
New Paradigm ◽  
New Class ◽  
Paracrine Action ◽  
Prostate Tumor Cells

scholarly journals Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Ivy Chung ◽  
Kun Zhou ◽  
Courtney Barrows ◽  
Jacqueline Banyard ◽  
Arianne Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Metastatic Prostate Cancer ◽  
Prostate Tumor ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Prostate Tumor Cells ◽  
Benign Prostate

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients’ prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases – two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

scholarly journals Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells

2017 ◽  
Vol 42 (4) ◽  
pp. 1366-1376 ◽  
Author(s):  
Matias Julian Stagno ◽  
Nefeli Zacharopoulou ◽  
Jonas Bochem ◽  
Anna Tsapara ◽  
Lisann Pelzl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Enzyme Inhibitor ◽  
Specific Inhibitor ◽  
Prostate Tumor ◽  
Cancer Drug ◽  
Prostate Cancer Cells ◽  
Prostate Tumor Cells

Background/Aims: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells. Methods: Migration was assessed by transwell and wound healing assays, Orai1 and Stim1 abundance by RT-PCR and confocal immunofluorescence microscopy, Fura-2 fluorescence was utilized to determine intracellular Ca2+ and Western blotting for FAK/pFAK measurements. Results: We observed strong inhibition of cell migration in istaroxime treated DU-145 prostate cancer cells. Istaroxime further decreased Orai1 and Stim1 transcript levels and downregulated Orai1 protein expression. Moreover, SOCE was significantly decreased upon istaroxime treatment. Furthermore, istaroxime strikingly diminished phosphorylated FAK levels. Interestingly, the efficacy of istaroxime on the inhibition of DU-145 cell migration was further enhanced by blocking Orai1 with 2-APB and FAK with the specific inhibitor PF-00562271. These results provide strong evidence that istaroxime prevents cell migration and motility of DU-145 prostate tumor cells, an effect at least partially attributed to Orai1 downregulation and FAK de-activation. Conclusion: Collectively our results indicate that this enzyme inhibitor, besides its pro-apoptotic action, affects motility of cancer cells, supporting its potential role as a strong candidate for further clinical cancer drug development.

scholarly journals Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder

2009 ◽  
Vol 16 (1) ◽  
pp. 123-137 ◽  
Author(s):  
Stephen A Boorjian ◽  
Hannelore V Heemers ◽  
Igor Frank ◽  
Sara A Farmer ◽  
Lucy J Schmidt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Urothelial Carcinoma ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Prostate Cancer Cells ◽  
Bladder Urothelium ◽  
Dependent Cell ◽  
Carcinoma Of The Bladder ◽  
Transcriptional Complex

Urothelial carcinoma (UC) of the bladder is approximately three times more common in men than women. While the etiology for this gender difference in incidence remains unknown, a role for androgen receptor (AR) signaling has been suggested. The mechanisms by which AR activity is regulated in UC cells, however, are largely elusive. Here, we explore the significance of coregulators that are critical for the formation of a functional AR transcriptional complex, in UC cells. Using two AR-positive UC cell lines, TCC-SUP and UMUC3, we demonstrate the expression of the coactivators NCOA1, NCOA2, NCOA3, CREBBP, and EP300 in UC cells. small interfering RNA-mediated knockdown of the AR or any of these coactivators markedly impacted cell viability and abrogated androgen-dependent cell proliferation. Noteworthy, contrary to AR-positive prostate cancer cells, expression of these AR-associated coactivators was not androgen regulated in UC cells. To assess the clinical relevance of coactivator expression, we performed immunohistochemistry on paraffin-embedded sections from 55 patients with UC of the bladder. We found that while 24 out of 55 (44%) of tumors expressed the AR, each of the coactivators was expressed by 85–100% of the bladder cancers. Moreover, we noted a significant downregulation of NCOA1 expression in tumors versus adjacent, non-tumor bladder urothelium, with a mean of 68% (range 0–100) of tumor cells demonstrating NCOA1 staining versus a mean of 81% (range 0–90) of non-tumor cells (P=0.03). Taken together, our data suggest an important role for AR-associated coactivators in UC and point toward differences in the regulation of AR activity between bladder and prostate cancer cells.

scholarly journals Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer Cells

2018 ◽  
Vol 24 ◽  
pp. 7051-7056 ◽  
Author(s):  
Shuaibin Wang ◽  
Sen Yang ◽  
Cunjin Nan ◽  
Yijun Wang ◽  
Youhua He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Prostate Cancer Cells

609: Effects of Sirna and Phytoestrogen Treatments on the Expression of Genes Regulated through the Androgen Receptor of Lncap Prostate Cancer Cells

2004 ◽  
Vol 171 (4S) ◽  
pp. 162-162
Author(s):  
Paul Thelen ◽  
Michal Grzmil ◽  
Iris E. Eder ◽  
Barbara Spengler ◽  
Peter Burfeind ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Expression Of Genes
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