- Authors:
- O. Orellana-Serradell
- C. E. Poblete
- C. Sanchez
- E. A. Castellón
- I. Gallegos
- C. Huidobro
- M. N. Llanos
- H. R. Contreras
- Corresponding author:
- H. R. Contreras [ hcontrer@med.uchile.cl ]
- View Affiliations
-
Published online on: Wednesday, January 21, 2015
- DOI: 10.3892/or.2015.3746
Abstract
In the early stages, prostate cancer is androgen‑ dependent;
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.
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