Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer

Detalhes bibliográficos
Autor(a) principal: Tuszynski, Jack
Data de Publicação: 2017
Outros Autores: Tilli, Tatiana M., Levin, Michael
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/59336
Resumo: Department of Oncology. Faculty of Medicine and Dentistry. University of Alberta. Edmonton, Canada / Department of Physics. University of Alberta. Edmonton, Canada.
id CRUZ_3d9bf688f702c7aeebbd7aad2763c5e5
oai_identifier_str oai:www.arca.fiocruz.br:icict/59336
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Tuszynski, JackTilli, Tatiana M.Levin, Michael2023-06-30T20:58:43Z2023-06-30T20:58:43Z2017TUSZYNSKI, Jack; TILLI, Tatiana M.; LEVIN, Michael. Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer. Current Pharmaceutical Design, v. 23, n. 32, p. 4827-4841, 2017.1381-6128https://www.arca.fiocruz.br/handle/icict/5933610.2174/13816128236661705301058371873-4286engBentham Science PublishersAnimalsAntineoplastic AgentsBioelectric Energy SourcesCell ProliferationCell SurvivalFluoxetineHumansIon ChannelsNeoplasmsNeurotransmitter AgentsSerotonin Uptake InhibitorsIon channelsSerotoninNeurotransmitterBioelectricityBiophysicsResting potentialProzacSSRIIon channel and neurotransmitter modulators as electroceutical approaches to the control of cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Oncology. Faculty of Medicine and Dentistry. University of Alberta. Edmonton, Canada / Department of Physics. University of Alberta. Edmonton, Canada.Biology Department. Allen Discovery Center. Tufts University. Medford, USA.Fundação Oswaldo Cruz. Center for Technological Development in Health. National Institute for Science and Technology on Innovation in Neglected Diseases. Laboratory of Biological System Modeling. Rio de Janeiro, RJ, Brasil.The activities of individual cells must be tightly coordinated in order to build and maintain complex 3- dimensional body structures during embryogenesis and regeneration. Thus, one way to view cancer is within systems biology as a network disorder affecting the ability of cells to properly interact with a morphodynamic field of instructive signals that keeps proliferation and migration orchestrated toward the anatomical needs of the host organism. One layer of this set of instructive microenvironmental cues is bioelectrical. Voltage gradients among all somatic cells (not just excitable nerve and muscle) control cell behavior, and the ionic coupling of cells into networks via electrochemical synapses allows them to implement tissue-level patterning decisions. These gradients have been increasingly implicated in the induction and suppression of tumorigenesis and metastasis, in the emerging links between developmental bioelectricity to the cancer problem. Consistent with the well-known role of neurotransmitter molecules in transducing electrical activity to downstream cascades in the brain, serotonergic signaling has likewise been implicated in cancer. Here, we review these recent data and propose new approaches for manipulating bioelectric and neurotransmitter pathways in cancer biology based on a bioelectric view of cancer. To support this methodology, we present new data on the effects of the SSRI Prozac and its analog (ZINC ID = ZINC06811610) on survival of both cancer (MCF7) and normal (MCF10A) breast cells exposed to these compounds. We found an IC50 concentration (25 µM for Prozac and 100 µM for the Prozac analog) at which these compounds inhibited tumor cell survival and proliferation. Additionally, at these concentrations, we did not observe alterations in a non-tumoral cell line. This constitutes a proof-of-concept demonstration for our hypothesis that the use of both existing and novel drugs as electroceuticals could serve as an alternative to highly toxic chemotherapy strategies replacing or augmenting them with less toxic alternatives. We believe this new approach forms an exciting roadmap for future biomedical advances.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/59336/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINAL10.2174_1381612823666170530105837.pdfapplication/pdf9406240https://www.arca.fiocruz.br/bitstream/icict/59336/2/10.2174_1381612823666170530105837.pdf9c83732a4c6ba8ed756ffe3220ad0480MD52icict/593362023-07-01 22:02:26.923oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-07-02T01:02:26Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
title Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
spellingShingle Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
Tuszynski, Jack
Animals
Antineoplastic Agents
Bioelectric Energy Sources
Cell Proliferation
Cell Survival
Fluoxetine
Humans
Ion Channels
Neoplasms
Neurotransmitter Agents
Serotonin Uptake Inhibitors
Ion channels
Serotonin
Neurotransmitter
Bioelectricity
Biophysics
Resting potential
Prozac
SSRI
title_short Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
title_full Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
title_fullStr Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
title_full_unstemmed Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
title_sort Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer
author Tuszynski, Jack
author_facet Tuszynski, Jack
Tilli, Tatiana M.
Levin, Michael
author_role author
author2 Tilli, Tatiana M.
Levin, Michael
author2_role author
author
dc.contributor.author.fl_str_mv Tuszynski, Jack
Tilli, Tatiana M.
Levin, Michael
dc.subject.mesh.en_US.fl_str_mv Animals
Antineoplastic Agents
Bioelectric Energy Sources
Cell Proliferation
Cell Survival
Fluoxetine
Humans
Ion Channels
Neoplasms
Neurotransmitter Agents
Serotonin Uptake Inhibitors
topic Animals
Antineoplastic Agents
Bioelectric Energy Sources
Cell Proliferation
Cell Survival
Fluoxetine
Humans
Ion Channels
Neoplasms
Neurotransmitter Agents
Serotonin Uptake Inhibitors
Ion channels
Serotonin
Neurotransmitter
Bioelectricity
Biophysics
Resting potential
Prozac
SSRI
dc.subject.en.en_US.fl_str_mv Ion channels
Serotonin
Neurotransmitter
Bioelectricity
Biophysics
Resting potential
Prozac
SSRI
description Department of Oncology. Faculty of Medicine and Dentistry. University of Alberta. Edmonton, Canada / Department of Physics. University of Alberta. Edmonton, Canada.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2023-06-30T20:58:43Z
dc.date.available.fl_str_mv 2023-06-30T20:58:43Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv TUSZYNSKI, Jack; TILLI, Tatiana M.; LEVIN, Michael. Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer. Current Pharmaceutical Design, v. 23, n. 32, p. 4827-4841, 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/59336
dc.identifier.issn.en_US.fl_str_mv 1381-6128
dc.identifier.doi.none.fl_str_mv 10.2174/1381612823666170530105837
dc.identifier.eissn.none.fl_str_mv 1873-4286
identifier_str_mv TUSZYNSKI, Jack; TILLI, Tatiana M.; LEVIN, Michael. Ion channel and neurotransmitter modulators as electroceutical approaches to the control of cancer. Current Pharmaceutical Design, v. 23, n. 32, p. 4827-4841, 2017.
1381-6128
10.2174/1381612823666170530105837
1873-4286
url https://www.arca.fiocruz.br/handle/icict/59336
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/59336/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/59336/2/10.2174_1381612823666170530105837.pdf
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
9c83732a4c6ba8ed756ffe3220ad0480
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1798324870362169344

Registros relacionados