7 research outputs found
miR-429 suppresses cell growth and induces apoptosis of human thyroid cancer cell by targeting ZEB1
Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells
© 2019 Spandidos Publications. All rights reserved.Prostate cancer (PCa) is the second most common type of male malignancy worldwide. The transcription factor zinc finger E-box binding homeobox 1 (ZEB1) is associated with epithelial-mesenchymal transition and is also involved in regulation of androgen receptor (AR) expression, the main ligands of which are testosterone and dihydrotestosterone (DHT). These androgens are synthesized through the steroidogenic pathway within the prostate, and their synthesis is altered in PCa. The present study aimed to determine the ZEB1-induced alterations in androgen synthesis and AR expression in the DU145 PCa cell line. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunocytochemistry were used to determine the mRNA and protein expression levels, and cellular localization of steroidogenic pathway enzymes in the DU145 cell line in response to ZEB1 silencing. Furthermore, the concentrations of testosterone and DHT w
Proapoptotic effect of endocannabinoids in prostate cancer cells
Artículo de publicación ISIIn the early stages, prostate cancer is androgendependent;
therefore, medical castration has shown significant
results during the initial stages of this pathology. Despite this
early effect, advanced prostate cancer is resilient to such treatment.
Recent evidence shows that derivatives of Cannabis
sativa and its analogs may exert a protective effect against
different types of oncologic pathologies. The purpose of the
present study was to detect the presence of cannabinoid receptors
(CB1 and CB2) on cancer cells with a prostatic origin and
to evaluate the effect of the in vitro use of synthetic analogs. In
order to do this, we used a commercial cell line and primary
cultures derived from prostate cancer and benign prostatic
hyperplasia. The presence of the CB1 and CB2 receptors
was determined by immunohistochemistry where we showed
a higher expression of these receptors in later stages of the
disease (samples with a high Gleason score). Later, treatments
were conducted using anandamide, 2-arachidonoyl
glycerol and a synthetic analog of anandamide, methanandamide.
Using the MTT assay, we proved that the treatments
produced a cell growth inhibitory effect on all the different
prostate cancer cultures. This effect was demonstrated to be
dose-dependent. The use of a specific CB1 receptor blocker
(SR141716) confirmed that this effect was produced primarily
from the activation of the CB1 receptor. In order to understand
the MTT assay results, we determined cell cycle distribution by
flow cytometry, which showed no variation at the different cell
cycle stages in all the cultures after treatment. Treatment with
endocannabinoids resulted in an increase in the percentage of
apoptotic cells as determined by Annexin V assays and caused
an increase in the levels of activated caspase-3 and a reduction
in the levels of Bcl-2 confirming that the reduction in cell
viability noted in the MTT assay was caused by the activation
of the apoptotic pathway. Finally, we observed that endocannabinoid
treatment activated the Erk pathway and at the same
time, produced a decrease in the activation levels of the Akt
pathway. Based on these results, we suggest that endocannabinoids
may be a beneficial option for the treatment of prostate
cancer that has become nonresponsive to common therapies.Vicerrectoria de Investigacion y Desarrrollo of Universidad de Chile (VID)
DI MULT 05/36-2
FONDECYT
1060500
1110269
1140417
Grant DI MULT 05/36-2. Grants FONDECYT, 1060500 (H.C.),
1110269 (H.C.) and 1140417 (E.C.)