New Insight on the Role of Transient Receptor Potential (TRP) Channels in Driven Gliomagenesis Pathways

Santoni, Giorgio; Morelli, Maria Beatrice; Amantini, Consuelo; Santoni, Matteo; Nabissi, Massimo

doi:10.5772/24789

Cited by 2 publications

(1 citation statement)

References 143 publications

(123 reference statements)

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“…Although new therapeutic options have been developed on the basis of new knowledge about the molecular nature of GBM, surgery in association with radiation therapy and chemotherapy remains the standard of care. Several reports demonstrated the important role played by ion channels belonging to the transient receptor potential (TRP) superfamily in GBM [3,4].…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

Morelli

Amantini

Tomassoni

et al. 2019

Cancers

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A link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma patients and two human glioblastoma cell lines and compared to normal human brain, astrocytes, and epileptic tissues. The subcellular distribution of TRPML-1 was examined via confocal microscopy in the glioma cell lines. Then, to assess the role of TRPML-1, cell viability assays have been conducted in T98 and U251 cell lines treated with the specific TRPML-1 agonist, MK6-83. We found that MK6-83 reduced cell viability and induced caspase-3-dependent apoptosis. Indeed, the TRPML-1 silencing or the blockage of TRPML-1 dependent [Ca2+]i release abrogated these effects. In addition, exposure of glioma cells to the reactive oxygen species (ROS) inducer, carbonyl cyanide m-chlorophenylhydrazone (CCCP), stimulated a TRPML-1-dependent autophagic cell death, as demonstrated by the ability of the autophagic inhibitor bafilomycin A, the TRPML-1 inhibitor sphingomyelin, and the TRPML-1 silencing to completely inhibit the CCCP-mediated effects. To test a possible correlation with patient’s survival, Kaplan–Meier, univariate, and multivariate analysis have been performed. Data showed that the loss/reduction of TRPML-1 mRNA expression strongly correlates with short survival in glioblastoma (GBM) patients, suggesting that the reduction of TRPML-1 expression represents a negative prognostic factor in GBM patients.

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Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

Morelli

Amantini

Tomassoni

et al. 2019

Cancers

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Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents

et al. 2012

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The aggressive behavior of Glioblastoma multiforme (GBM) is mainly due to high invasiveness and proliferation rate as well as to high resistance to standard chemotherapy. Several chemotherapeutic agents like temozolomide (TMZ), carmustine (BCNU) or doxorubicin (DOXO) have been employed for treatment of GBM, but they display limited efficacy. Therefore, it is important to identify new treatment modalities to improve therapeutic effects and enhance GBM chemosensitivity. Recently, activation of the transient receptor potential vanilloid type 2 (TRPV2) has been found to inhibit human GBM cell proliferation and overcome BCNU resistance of GBM cells. Herein, we evaluated the involvement of cannabidiol (CBD)-induced TRPV2 activation, in the modulation of glioma cell chemosensitivity to TMZ, BCNU and DOXO. We found that CBD increases TRPV2 expression and activity. CBD by triggering TRPV2-dependent Ca(2+) influx increases drug uptake and synergizes with cytotoxic agents to induce apoptosis of glioma cells, whereas no effects were observed in normal human astrocytes. Moreover, as the pore region of transient receptor potential (TRP) channels is critical for ion channel permeation, we demonstrated that deletion of TRPV2 poredomain inhibits CBD-induced Ca(2+) influx, drug uptake and cytotoxic effects. Overall, we demonstrated that co-administration of cytotoxic agents together with the TRPV2 agonist CBD increases drug uptake and parallelly potentiates cytotoxic activity in human glioma cells.

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New Insight on the Role of Transient Receptor Potential (TRP) Channels in Driven Gliomagenesis Pathways

Cited by 2 publications

References 143 publications

Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents

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