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Research ArticleMinireview—A Latin American Perspective on Ion Channels

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Fernanda B. Morrone, Marina P. Gehring and Natália F. Nicoletti
Molecular Pharmacology September 2016, 90 (3) 403-409; DOI: https://doi.org/10.1124/mol.116.103770
Fernanda B. Morrone
Programa de Pós-graduação em Biologia Celular e Molecular (F.B.M., M.P.G., N.F.N), Programa de Pós-graduação em Medicina e Ciências da Saúde, Faculdade de Farmácia, Pontifícia Universidade Católica do RS, Porto Alegre (F.B.M.); Laboratório de Terapia Celular, Centro de Ciências Biológicas e da Saúde, Universidade de Caxias do Sul, Caxias do Sul (N.F.N.), Brasil
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Marina P. Gehring
Programa de Pós-graduação em Biologia Celular e Molecular (F.B.M., M.P.G., N.F.N), Programa de Pós-graduação em Medicina e Ciências da Saúde, Faculdade de Farmácia, Pontifícia Universidade Católica do RS, Porto Alegre (F.B.M.); Laboratório de Terapia Celular, Centro de Ciências Biológicas e da Saúde, Universidade de Caxias do Sul, Caxias do Sul (N.F.N.), Brasil
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Natália F. Nicoletti
Programa de Pós-graduação em Biologia Celular e Molecular (F.B.M., M.P.G., N.F.N), Programa de Pós-graduação em Medicina e Ciências da Saúde, Faculdade de Farmácia, Pontifícia Universidade Católica do RS, Porto Alegre (F.B.M.); Laboratório de Terapia Celular, Centro de Ciências Biológicas e da Saúde, Universidade de Caxias do Sul, Caxias do Sul (N.F.N.), Brasil
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Abstract

Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca2+ activity plays an important role in the regulation of cell proliferation, and Ca2+ signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca2+ by modulating the driving force for Ca2+ entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca2+-influx and an indirect activator of voltage-gated Ca2+-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca2+, and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

Footnotes

    • Received February 14, 2015.
    • Accepted July 11, 2016.
  • dx.doi.org/10.1124/mol.116.103770.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 90 (3)
Molecular Pharmacology
Vol. 90, Issue 3
1 Sep 2016
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Research ArticleMinireview—A Latin American Perspective on Ion Channels

Calcium Channels in Malignant Brain Tumors

Fernanda B. Morrone, Marina P. Gehring and Natália F. Nicoletti
Molecular Pharmacology September 1, 2016, 90 (3) 403-409; DOI: https://doi.org/10.1124/mol.116.103770

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Research ArticleMinireview—A Latin American Perspective on Ion Channels

Calcium Channels in Malignant Brain Tumors

Fernanda B. Morrone, Marina P. Gehring and Natália F. Nicoletti
Molecular Pharmacology September 1, 2016, 90 (3) 403-409; DOI: https://doi.org/10.1124/mol.116.103770
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    • Voltage-Gated Calcium Channels
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