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
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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