The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells
Autor: | Ágata Ramos-Torres, Inés Díaz-Laviada, Cecilia Morell, D Vara, Nieves Rodríguez-Henche, Alicia Bort |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_treatment Gene Expression AMP-Activated Protein Kinases Neuroendocrine tumors urologic and male genital diseases Neuroendocrine differentiation Receptor Cannabinoid CB2 Mice Phosphatidylinositol 3-Kinases Prostate cancer 0302 clinical medicine Receptor Cannabinoid CB1 WIN 55 212-2 TOR Serine-Threonine Kinases Neuroendocrine Tumors Cell Transformation Neoplastic 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Original Article Signal Transduction medicine.drug PCA3 medicine.medical_specialty Morpholines Urology Naphthalenes Models Biological 03 medical and health sciences Cell Line Tumor Internal medicine LNCaP medicine Animals Humans business.industry Prostatic Neoplasms medicine.disease Benzoxazines Disease Models Animal 030104 developmental biology Cancer research Cannabinoid Benign prostatic hyperplasia (BPH) business Proto-Oncogene Proteins c-akt Biomarkers |
Zdroj: | Prostate Cancer and Prostatic Diseases |
ISSN: | 1476-5608 1365-7852 |
Popis: | BACKGROUND: Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells. METHODS: NE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA. RESULTS: The differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases. CONCLUSIONS: Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer. |
Databáze: | OpenAIRE |
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