Proapoptotic impact of endocannabinoids in prostate cancer cells
In the early stages, prostate cancer is androgen‑ dependent thus, health-related castration has shown important final results throughout the initial stages of this pathology. Regardless of this early impact, sophisticated prostate cancer is resilient to such therapy. Current proof shows that derivatives of Cannabis sativa and its analogs might exert a protective impact against distinct varieties of oncologic pathologies. The goal 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 impact of the in vitro use of synthetic analogs. In order to do this, we utilized a industrial cell line and key cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry exactly where we showed a larger expression of these receptors in later stages of the illness (samples with a higher Gleason score). Later, treatment options had been carried out employing anandamide, two-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Employing the MTT assay, we proved that the treatment options made a cell development inhibitory impact on all the distinct prostate cancer cultures. This impact was demonstrated to be dose-dependent. The use of a distinct CB1 receptor blocker (SR141716) confirmed that this impact was made mostly from the activation of the CB1 receptor. In order to realize the MTT assay final results, we determined cell cycle distribution by flow cytometry, which showed no variation at the distinct cell cycle stages in all the cultures after therapy. Therapy with endocannabinoids resulted in an enhance in the percentage of apoptotic cells as determined by Annexin V assays and triggered an enhance in the levels of activated caspase-three and a reduction in the levels of Bcl-two confirming that the reduction in cell viability noted in the MTT assay was triggered by the activation of the apoptotic pathway. Ultimately, we observed that endocannabinoid therapy activated the Erk pathway and at the similar time, made a lower in the activation levels of the Akt pathway. Primarily based on these final results, we recommend that endocannabinoids might be a advantageous selection for the therapy of prostate cancer that has turn into nonresponsive to prevalent therapies.
Orellana-Serradell O1, Poblete CE1, Sanchez C1, Castellón EA1, Gallegos Itwo, Huidobro Cthree, Llanos MNfour, Contreras HR1.
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