Abstract
Osteosarcoma is the most common and aggressive bone tumor in children. The Endocannabinoid/Endovanilloid system has been proposed as anticancer target in tumor of different origins. This system is composed of two receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells. We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay. We also compared the effects of these compounds on Caspase-3, AKT, MMP-2 and Notch-1 regulation by Q-PCR and Western Blotting.We observed an anti-proliferative, pro-apoptotic, anti-invasive effect. Our results show that both CB2 stimulation and TRPV1 activation, in different Osteosarcoma cell lines, can act on the same pathways to obtain the same effect, indicating the Endocannabinoid/Endovanilloid system as a new therapeutic target in Osteosarcoma.
Highlights
Osteosarcoma (OS), the most common primary malignant tumor of bone, affects predominantly children and adolescents, exhibiting high invasion and metastasis rate [1, 2]
We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay
We investigated for the first time the expression of CB2 and Transient Potential Vanilloid 1 (TRPV1) receptors and the effects of JWH-133 and RTX, at different concentrations, in six OS cell lines (Saos-2, MG-63, MNNG/HOS, KHOS/NP, Hs888Lu and U-2 OS), analyzing the response to these compounds on cell survival, invasion and migration capacity
Summary
Osteosarcoma (OS), the most common primary malignant tumor of bone, affects predominantly children and adolescents, exhibiting high invasion and metastasis rate [1, 2]. Due to a high frequency of systemic spread at the early phase and the strong chemotherapy resistance, the five-year survival rate remains at only 20%. Available treatments results in significant morbidity (cardiac toxicity, infertility, renal dysfunction) and chemo-resistance [3,4,5,6]. OS patients present a decrease in bone mass density (BMD) during chemotherapy, and in long-term survivors osteoporosis and fractures are frequently present [7, 8]. During the last 10 years mounting evidence has placed mesenchimal stem cells (MSCs) and/or their immediate lineage progenitors as the most likely cell-oforigin for many types of sarcomas including OS [9,10,11]
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