scholarly journals Selenium Biomarkers in Prostate Cancer Cell Lines and Influence of Selenium on Invasive Potential of PC3 Cells

2013 ◽  
Vol 3 ◽  
Author(s):  
Wouter Hendrickx ◽  
Julie Decock ◽  
Francis Mulholland ◽  
Yongping Bao ◽  
Susan Fairweather-Tait
Author(s):  
Fatemeh Akbarian ◽  
Farid Dadkhah ◽  
Arezoo Campbel ◽  
Farrokh Asadi ◽  
Ghasem Ahangari

Background: Dopamine receptor (DR) gene family play an essential role in the regulation of interleukin-6 (IL-6) production. Our prior analysis of human prostate biopsy samples demonstrated the increased expression of IL-6 and a down regulating trend for dopamine receptor gene family. Objective: The objective was to investigate the expression of dopamine receptors, their catabolizing enzyme and IL-6 in prostate cancer cell lines and assess pharmacological effect of dopamine receptor modulators as a novel class of drugs repurposed for treatment of prostate cancer. Methods: The therapeutic effect of dopamine, DR agonists, and DR antagonist were examined using LNCaP and PC3 cell lines.CellviabilityandproliferationwereassessedbyMTTassayandproliferatingcellnuclearantigenexpressionanalysis, respectively. Furthermore, bax/bcl2 ratio, immunofluorescence assay and flow cytometric assay were performed for apoptosis analysis. RT-q PCR analysis was used to characterize relative expression of dopamine-related genes, catabolic enzyme catechol-o-methyl-transferase (COMT) and IL-6 before and after treatment to assess the therapeutic effects of drugs. Results: LNCaP cells express DRD1, DRD2, DRD5 and COMT genes and PC3 cells only express IL-6 gene. In-vitro, dopamine receptor agonists reduced cell viability of LNCaP and PC3 cells. In contrast, dopamine and dopamine receptor antagonist significantly increased tumor growth in PC3 cells. Conclusion: Our results offer novel suggestion for a pathogenic role of dopamine receptor signaling in prostate cancer adenocarcinoma and indicates that modulators of DR-IL-6 pathway, including FDA-approved drug bromocriptine, might be utilized as novel drug repurposing strategy.


The Prostate ◽  
2013 ◽  
Vol 73 (10) ◽  
pp. 1082-1089 ◽  
Author(s):  
Chen Zhu ◽  
Jie Li ◽  
Qi Ding ◽  
Gong Cheng ◽  
Hai Zhou ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21135-21135
Author(s):  
M. Toledo Lobo ◽  
M. Arenas Jiménez ◽  
L. Huertas Martínez ◽  
S. Sacristán lópez ◽  
A. Moyano Jato ◽  
...  

21135 Background: The mechanism through wich zoledronic acid exerts its activity is poorly understood. Low density lipoprotein receptor (LDLR) and scavenger receptor class B type 1 (SRBI) overproduction is an important mechanism in cancer cells for obtaining more essential fatty acids and cell growth. The effects of in vitro zoledronate treatment on the lipid metabolism of prostate cancer cell lines were studied. Methods: Three prostatic cancer cell lines, androgen insensitive PC3, androgen dependent low-passage (LP) LNCaP and androgen independent high-passage (HP) LNCaP cells were studied. Cells were plated either in RPMI with 5% foetal calf serum and lipoprotein depleted serum (LPDS) and were treated with zoledronate at different concentrations. The lipid transporters profile was analyzed by western blotting for LDLR and SRB1. Results: The same LDLR bands profile was observed in all cell lines, 160 and 105 kDa. The basal levels of LDLR were higher in the PC3 cells. Zoledronate therapy induced LDLR expression in all cell lines but PC3 were less sensitive to this effect. Cells cultured with LPDS showed an enhanced expression of LDLR and PC3 cells were less sensitive to this effect. HP LNCaP cells were the most affected by lipoprotein deprivation however this effect diminished 72 hours after treatment. The bands profile for SRBI consisted of a 65 kDa predominant band and a 40 kDa band in both LP/HP LNCaP cells. In PC3 cells main band was located in 65 kDa and accessory band in 30kDa. The basal levels of the 65kDa band were higher in HP than in LP LNCaP or PC3 cells and zoledronate therapy caused a dose- dependent induction in HP LNCaP and dose-dependent reduction in PC3 cells, LP LNCaP cells were resistant to the treatment. LPDS induced SRBI levels in all cell lines inverting the effect caused by zoledronate in HP LNCaP cells in complete culture medium and at high doses (100μM) a complete inhibition of SRBI protein was found. Low molecular weight bands changed in the same way as the 65 kDa band. Conclusions: LDL-R and SRBI have been isolated in prostate cancer cell lines. Based on previous cell growth studies, the lipid transporters profile might be significantly involved in the resistance to zoledronate therapy. Lipoprotein regulation pathways should be considered in the therapy of metastatic prostate cancer. No significant financial relationships to disclose.


Cell Cycle ◽  
2011 ◽  
Vol 10 (7) ◽  
pp. 1121-1131 ◽  
Author(s):  
Giuditta Viticchiè ◽  
Anna Maria Lena ◽  
Alessia Latina ◽  
Amanda Formosa ◽  
Lea H. Gregersen ◽  
...  

2006 ◽  
Vol 175 (4S) ◽  
pp. 258-258
Author(s):  
Ruth Schwaninger ◽  
Cyrill A. Rentsch ◽  
Antoinette Wetterwald ◽  
Irena Klima ◽  
Gabri Van der Pluijm ◽  
...  

1992 ◽  
Vol 68 (06) ◽  
pp. 662-666 ◽  
Author(s):  
W Hollas ◽  
N Hoosein ◽  
L W K Chung ◽  
A Mazar ◽  
J Henkin ◽  
...  

SummaryWe previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.


Sign in / Sign up

Export Citation Format

Share Document