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

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, 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, a malignancy characterized by the accumulation of immature cells.Methods: FACS analysis, Western blot analysis, gene silencing, and cell viability assay were performed to investigate the activation of transient receptor potential vanilloid 1, by N-oleoyl-dopamine, in chronic myeloid leukemia cell lines.Results: We demonstrated that the triggering of transient receptor potential vanilloid 1 inhibits cell growth and promotes apoptosis of chronic myeloid leukemia cells. Its activation induced calcium influx, oxidative stress, ER stress, mitochondria dysfunction, and caspase activation. Interestingly, a synergistic effect exerted by N-oleoyl-dopamine and the standard drug imatinib was found.Conclusion: Overall, our results support that transient receptor potential vanilloid 1 activation could be a promising strategy to enhance conventional therapy and improve the management of chronic myeloid leukemia.

“ThermoTRP” Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist)

“…Similar, the mitochondrial TRPV1-mediated "death mechanism" may also operate in cancer cells. In keeping with this, in chronic myeloid leukemia cells, TRPV1 activation can induce apoptosis via Ca 2+ influx, mitochondrial dysfunction, and caspase activation [17].…”

Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors

“…Calcium influx, OS, ER stress, mitochondrial failure, and caspase activation were all brought on by its activation. Remarkably, it was discovered that N-oleoyl-dopamine and the common medication imatinib worked in concert [123].…”

Advances in the role of ion channels in leukemia

“…TRPV1 can inhibit the growth of chronic myeloid cells and promote leukemia cell apoptosis, and its activation can induce calcium influx, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and caspase activation. Therefore, activating TRPV1 can enhance conventional treatments and improve the management of chronic myeloid leukemia [ 48 ]. TRPV5 and TRPV6 are highly expressed in malignant states of human lymphocytes and leukemia Jurkat T cells, where they regulate cell proliferation [ 49 ].…”