Salmonella–Host Cell Interactions, Changes in Host Cell Architecture, and Destruction of Prostate Tumor Cells with Genetically AlteredSalmonella

Increasingly, genetically modifiedSalmonellaare being explored as a novel treatment for cancer becauseSalmonellapreferentially replicate within tumors and destroy cancer cells without causing the septic shock that is typically associated with wild-typeS. typhimuriuminfections. However, the mechanisms by which genetically modifiedSalmonellastrains preferentially invade cancer cells have not yet been addressed in cellular detail. Here we present data that showS. typhimuriumstrains VNP20009, LT2, and CRC1674 invasion of PC-3M prostate cancer cells.S. typhimurium-infected PC-3M human prostate cancer cells were analyzed with immunofluorescence microscopy and transmission electron microscopy (TEM) at various times after inoculation. We analyzed microfilaments, microtubules, and DNA with fluorescence and immunofluorescence microscopy. 3T3 Phi-Yellow-mitochondria mouse 3T3 cells were used to study the effects ofSalmonellainfestation on mitochondria distribution in live cells. Our TEM results show gradual destruction of mitochondria within the PC-3M prostate cancer cells with complete loss of cristae at 8 h after inoculation. The fluorescence intensity in YFP-mitochondria-transfected mouse 3T3 cells decreased, which indicates loss of mitochondria structure. Interestingly, the nucleus does not appear affected bySalmonellawithin 8 h. Our data demonstrate that genetically modifiedS. typhimuriumdestroy PC-3M prostate cancer cells, perhaps by preferential destruction of mitochondria.

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

Frontiers in Oncology ◽

10.3389/fonc.2020.594141 ◽

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.

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Human selenium binding protein-1 (hSP56) inhibits anchorage-independent growth of PC-3 human prostate cancer cells and is down-regulated in primary human prostate tumor cells

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.9564 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 9564-9564 ◽

Cited By ~ 1

Author(s):

A. J. Sytkowski ◽

C. Gao ◽

L. Feldman ◽

C. Chen

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Prostate Tumor ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Anchorage Independent Growth ◽

Prostate Tumor Cells ◽

Human Prostate Tumor

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

Cellular Physiology and Biochemistry ◽

10.1159/000479200 ◽

2017 ◽

Vol 42 (4) ◽

pp. 1366-1376 ◽

Cited By ~ 3

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.

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

International Journal of Cancer ◽

10.1002/ijc.22830 ◽

2007 ◽

Vol 121 (6) ◽

pp. 1238-1244 ◽

Cited By ~ 24

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

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Electrochemical Detection of H2O2 Released from Prostate Cancer Cells Using Pt Nanoparticle-Decorated rGO–CNT Nanocomposite-Modified Screen-Printed Carbon Electrodes

Chemosensors ◽

10.3390/chemosensors8030063 ◽

2020 ◽

Vol 8 (3) ◽

pp. 63

Author(s):

Seokyung Lee ◽

Young Ju Lee ◽

Jae Hyung Kim ◽

Gi-Ja Lee

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Reference Electrode ◽

Clinical Analysis ◽

Live Cells ◽

Prostate Cancer Cells ◽

Good Electrocatalytic Activity ◽

Reduced Graphene ◽

Co Reduction ◽

Screen Printed

In this study, we fabricated platinum nanoparticles (PtNP)-decorated, porous reduced graphene oxide (rGO)–carbon nanotube (CNT) nanocomposites on a PtNP-deposited screen-printed carbon electrode (PtNP/rGO–CNT/PtNP/SPCE) for detection of hydrogen peroxide (H2O2), which is released from prostate cancer cells LNCaP. The PtNP/rGO–CNT/PtNP/SPCE was fabricated by a simple electrochemical deposition and co-reduction method. In addition, the amperometric response of the PtNP/rGO–CNT/PtNP/SPCE electrode was evaluated through consecutive additions of H2O2 at an applied potential of 0.2 V (vs. Ag pseudo-reference electrode). As a result, the prepared PtNP/rGO–CNT/PtNP/SPCE showed good electrocatalytic activity toward H2O2 compared to bare SPCE, rGO–CNT/SPCE, PtNP/SPCE, and rGO–CNT/PtNP/SPCE. In addition, the PtNP/rGO–CNT/PtNP/SPCE electrode exhibited a sensitivity of 206 μA mM−1·cm−2 to H2O2 in a linear range of 25 to 1000 μM (R2 = 0.99). Moreover, the PtNP/rGO–CNT/PtNP/SPCE electrode was less sensitive to common interfering substances, such as ascorbic acid, uric acid, and glucose than H2O2. Finally, real-time monitoring of H2O2 released from LNCaP cells was successfully performed by this electrode. Therefore, we expect that the PtNP/rGO–CNT/PtNP/SPCE can be utilized as a promising electrochemical sensor for practical nonenzymatic detection of H2O2 in live cells or clinical analysis.

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