The effects of cannabidiol via TRPV2 channel in chronic myeloid leukemia cells and its combination with imatinib

Maggi, Federica; Morelli, Maria Beatrice; Tomassoni, Daniele; Marinelli, Oliviero; Aguzzi, Cristina; Zeppa, Laura; Nabissi, Massimo; Santoni, Giorgio; Amantini, Consuelo

doi:10.1111/cas.15257

Cited by 21 publications

(15 citation statements)

References 71 publications

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“…We recently demonstrated the expression of TRPV1 on K562, KU812, and MOLM-6 CML cell lines, common myeloid progenitors, normal myeloid cell enrichment, and PBMCs, respectively ( Maggi et al, 2022 ). To enhance our analysis of TRPV1 expression, we have also performed in silico analyses with datasets 6326/6610 from the Stemformatics database and GSE13159 from the GEO repository, demonstrating its expression in all types of leukemia cells ( Supplementary Figure S1A ).…”

Section: Resultsmentioning

confidence: 99%

“…In this tumor type, it has only been demonstrated that the activation of TRPV5 and TRPV6 promotes a Ca 2+ -dependent cell cycle arrest ( Heise et al, 2010 ), and the inhibition of TRPM7 impairs cell proliferation and stimulates erythroid differentiation in K562 cells ( Takahashi et al, 2018 ). In addition, we recently showed that TRPV2 activation induced mitophagy associated with cell growth inhibition and stemness reduction in chronic myeloid leukemia (CML) cells ( Maggi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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

Maggi

Morelli

Aguzzi

et al. 2023

Front. Mol. Biosci.

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Maggi

Morelli

Aguzzi

et al. 2023

Front. Mol. Biosci.

Self Cite

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“…Inspired by the fact that TRPV2 and TRPV4 have very similar gene sequences, Huang et al found that CBD interacts with residues on the S6 helix of TRPV4, thus suggesting that TRPV4 plays an important role in CBD inhibition of glioma ( Huang et al, 2021 ). Maggi et al confirmed using cell growth and other assays that CBD can inhibit the proliferation and cycle of chronic myeloid leukemia cells through the TRPV2 channel ( Maggi et al, 2022 ).…”

Section: Studies On Regulation Of Transient Receptor Potential Channe...mentioning

confidence: 99%

Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients

et al. 2022

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In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs.

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“…Cannabidiol exerts a synergistic effect with imatinib in imatinib-resistant CML cells. 354 In AML carrying FLT3-ITD, FLT-3-ITD molecules were detected in the autophagosome after induction of autophagy with the proteasome inhibitor bortezomib. It suggests that autophagy is involved in the posttranslational degradation of aberrant PTKs, and induction of autophagy is undoubtedly beneficial in this case.…”

Section: Mechanisms Of Tki Resistancementioning

confidence: 99%

Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

Yang

Wang

et al. 2022

Sig Transduct Target Ther

108

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Protein tyrosine kinases (PTKs) are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state, leading to carcinogenesis. Inhibiting the aberrant PTK function could inhibit tumor growth. Therefore, tyrosine kinase inhibitors (TKIs), target-specific inhibitors of PTKs, have been used in treating malignant tumors and play a significant role in targeted therapy of cancer. Currently, drug resistance is the main reason for limiting TKIs efficacy of cancer. The increasing studies indicated that tumor microenvironment, cell death resistance, tumor metabolism, epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance, besides the abnormal activation of PTK-related signaling pathways involved in gene mutations. Accordingly, it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer. Herein, we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance, aiming to provide a theoretical basis for improving the efficacy of TKIs.

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The effects of cannabidiol via TRPV2 channel in chronic myeloid leukemia cells and its combination with imatinib

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 21 publications

References 71 publications

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

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

Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients

Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

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