Oncotarget

Research Papers:

Effects of CB2 and TRPV1 receptors’ stimulation in pediatric acute T-lymphoblastic leukemia

Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D’ Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale and Francesca Rossi _

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Oncotarget. 2018; 9:21244-21258. https://doi.org/10.18632/oncotarget.25052

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Abstract

Francesca Punzo1,2, Iolanda Manzo2, Chiara Tortora2, Elvira Pota1, Velia D’ Angelo1, Giulia Bellini2, Alessandra Di Paola1, Federica Verace1, Fiorina Casale1 and Francesca Rossi1

1Department of Women, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy

2Department of Experimental Medicine, Division of Pharmacology “Leonardo Donatelli”, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy

Correspondence to:

Francesca Rossi, email: francesca.rossi@unicampania.it

Keywords: oncogene; MYB; SKI; transcriptional regulation; acute myeloid leukemia

Received: August 24, 2017     Accepted: March 21, 2018     Published: April 20, 2018

ABSTRACT

T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy.

The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1.

We treated T-ALL lymphoblasts derived from 4 patients and Jurkat cells with a selective agonist at CB2 receptor: JWH-133 [100 nM] and an agonist at TRPV1 calcium channel: RTX [5 uM] at 6, 12 and 24 hours. We analyzed the effect on apoptosis and Cell Cycle Progression by a cytofluorimetric assays and evaluated the expression level of several target genes (Caspase 3, Bax, Bcl-2, AKT, ERK, PTEN, Notch-1, CDK2, p53) involved in cell survival and apoptosis, by Real-Time PCR and Western Blotting.

We observed a pro-apoptotic, anti-proliferative effect of these compounds in both primary lymphoblasts obtained from patients with T-ALL and in Jurkat cell line. Our results show that both CB2 stimulation and TRPV1 activation, can increase the apoptosis in vitro, interfere with cell cycle progression and reduce cell proliferation, indicating that a new therapeutic approach to T-cell ALL might be possible by modulating CB2 and TRPV1 receptors.


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