Metallothionein isoform 3 expression inhibits cell growth and increases drug resistance of PC-3 prostate cancer cells

The Prostate ◽  
2002 ◽  
Vol 52 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Rana Dutta ◽  
Donald A. Sens ◽  
Seema Somji ◽  
Mary Ann Sens ◽  
Scott H. Garrett
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Metallothionein Isoform 3

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.

Material properties of disulfide-crosslinked hyaluronic acid hydrogels influence prostate cancer cell growth and metabolism

2020 ◽  
Vol 8 (42) ◽  
pp. 9718-9733
Author(s):  
Nicky W. Tam ◽  
Dudley Chung ◽  
Samuel J. Baldwin ◽  
Jeffrey R. Simmons ◽  
Lingling Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hyaluronic Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Material Properties ◽  
Prostate Cancer Cell ◽  
Prostate Cancer Cells ◽  
Cancer Cell Growth ◽  
Diffusion Limited ◽  
Metastatic Cells

Studying prostate cancer cells embedded in hyaluronic acid hydrogels provides insight on how metastatic cells might behave in diffusion-limited tissue microenvironments.

scholarly journals Inhibition of Recombining Binding Protein Suppressor of Hairless (RBPJ) Impairs the Growth of Prostate Cancer

2015 ◽  
Vol 36 (5) ◽  
pp. 1982-1990 ◽  
Author(s):  
Li Xue ◽  
Hecheng Li ◽  
Qi Chen ◽  
Zhenlong Wang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cancer Cells ◽  
Receptor Activation ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Prostate Cancer Cells ◽  
Cancer Cell Growth ◽  
Promising Therapeutic Approach

Background/Aims: Notch signaling pathway regulates cancer cell growth. RBPJ is a key transcription factor downstream of Notch receptor activation, whereas the role of RBPJ in carcinogenesis of prostate cancer is ill-defined. Methods: Here, we evaluated the effects of RBPJ inhibition on the growth of prostate cancer cells. We knocked down RBPJ in prostate cancer cells by a short hairpin interfering RNA (shRNA). We measured cell growth by an MTT assay. We analyzed the levels of cell-cycle-associated proteins by Western blot. Results: We found that shRNA for RBPJ efficiently inhibited RBPJ expression in prostate cancer cells, resulting in a significant decrease in the cell growth. Further, RBPJ-mediated cell-growth inhibition appeared to be resulting from alteration of cell-cycle inhibitors p21 and p27, cell-cycle activators CDK2, CDK4 and CyclinD1, and apoptosis-suppressor Bcl-2. Conclusion: Our data suggest that shRNA intervention of RBPJ expression could be a promising therapeutic approach for treating human prostate cancer.

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