AUTHOR=Maggi Federica , Morelli Maria Beatrice , Aguzzi Cristina , Zeppa Laura , Nabissi Massimo , Polidori Carlo , Santoni Giorgio , Amantini Consuelo 

TITLE=Calcium influx, oxidative stress, and apoptosis induced by TRPV1 in chronic myeloid leukemia cells: Synergistic effects with imatinib

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1129202

DOI=10.3389/fmolb.2023.1129202

ISSN=2296-889X

ABSTRACT=Introduction: Calcium flux is the master second messenger that influences the proliferation-apoptosis balance. The ability of calcium flux alterations to reduce cell growth, makes ion channels interesting targets for therapy. Among all, we focused on Transient Receptor Potential Vanilloid 1 (TRPV1), a ligand-gated cation channel with selectivity for calcium. Its involvement in hematological malignancies is poorly investigated especially in the field of chronic myeloid leukemia (CML), a hematologic malignancy characterized by the accumulation of immature cells.
Methods: By using FACS analysis, western blot analysis, gene silencing and cell viability assay, we investigated the activation of TRPV1, by N-oleoyl-dopamine (OLDA), in CML cell lines.
Results: We demonstrated that the triggering of TRPV1 inhibits cell growth and promotes apoptosis of CML cells. Its activation induced calcium influx, oxidative stress, ER stress, mitochondria dysfunction and caspase activation. Interestingly, a synergistic effect by OLDA and the standard drug imatinib was found. 
Conclusion: Overall, our results support that TRPV1 activation could be a promising strategy to enhance conventional therapy and improve management of CML.