Research Papers:

Anti-proliferative, pro-apoptotic and anti-invasive effect of EC/EV system in human osteosarcoma

Francesca Punzo, Chiara Tortora, Daniela Di Pinto, Iolanda Manzo, Giulia Bellini, Fiorina Casale and Francesca Rossi _

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Oncotarget. 2017; 8:54459-54471. https://doi.org/10.18632/oncotarget.17089

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Francesca Punzo1,2, Chiara Tortora1,2, Daniela Di Pinto1, Iolanda Manzo2, Giulia Bellini2, Fiorina Casale1 and Francesca Rossi1

1Department of Women, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy

2Department of Experimental Medicine, Division of Pharmacology “Leonardo Donatelli”, The Second University of Naples, 80138 Naples, Italy

Correspondence to:

Francesca Rossi, email: [email protected]

Keywords: EC/EV system, osteosarcoma, OS cell lines, RTX, JWH-133

Received: December 23, 2016     Accepted: February 28, 2017     Published: April 13, 2017


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.

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