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Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene

Because the emergence of drug resistance is a major limitation of current treatments for multiple myeloma (MM), it is necessary to continuously develop novel anticancer strategies. Here, using an inactivated Sendai virus (Hemagglutinating Virus of Japan; HVJ) envelope (HVJ-E), we discovered that inc...

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Autores principales: Jiang, Yingzhe, Saga, Kotaro, Miyamoto, Yasuhide, Kaneda, Yasufumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094981/
https://www.ncbi.nlm.nih.gov/pubmed/27145280
http://dx.doi.org/10.18632/oncotarget.9105
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author Jiang, Yingzhe
Saga, Kotaro
Miyamoto, Yasuhide
Kaneda, Yasufumi
author_facet Jiang, Yingzhe
Saga, Kotaro
Miyamoto, Yasuhide
Kaneda, Yasufumi
author_sort Jiang, Yingzhe
collection PubMed
description Because the emergence of drug resistance is a major limitation of current treatments for multiple myeloma (MM), it is necessary to continuously develop novel anticancer strategies. Here, using an inactivated Sendai virus (Hemagglutinating Virus of Japan; HVJ) envelope (HVJ-E), we discovered that increase of cytoplasmic Ca(2+) by virus-cell fusion significantly induced apoptosis against human MM cells but not peripheral blood mononuclear cells from healthy donors. Interaction of F protein of HVJ-E with MM cells increased intracellular Ca(2+) level of MMs by the induction of Ca(2+) efflux from endoplasmic reticulum but not influx from extracellular region. The elevation of the Ca(2+) cytoplasmic level induced SMAD1/5/8 phosphorylation and translocation into the nucleus, and SMAD1/5/8 and SMAD4 complex suppressed c-Myc transcription. Meanwhile, HVJ-E decreases S62 phosphorylation of c-Myc and promotes c-Myc protein degradation. Thus, HVJ-E-induced cell death of MM resulted from suppression of c-Myc by both destabilization of c-Myc protein and downregulation of c-Myc transcription. This study indicates that HVJ-E will be a promising tool for MM therapy.
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spelling pubmed-50949812016-11-22 Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene Jiang, Yingzhe Saga, Kotaro Miyamoto, Yasuhide Kaneda, Yasufumi Oncotarget Research Paper Because the emergence of drug resistance is a major limitation of current treatments for multiple myeloma (MM), it is necessary to continuously develop novel anticancer strategies. Here, using an inactivated Sendai virus (Hemagglutinating Virus of Japan; HVJ) envelope (HVJ-E), we discovered that increase of cytoplasmic Ca(2+) by virus-cell fusion significantly induced apoptosis against human MM cells but not peripheral blood mononuclear cells from healthy donors. Interaction of F protein of HVJ-E with MM cells increased intracellular Ca(2+) level of MMs by the induction of Ca(2+) efflux from endoplasmic reticulum but not influx from extracellular region. The elevation of the Ca(2+) cytoplasmic level induced SMAD1/5/8 phosphorylation and translocation into the nucleus, and SMAD1/5/8 and SMAD4 complex suppressed c-Myc transcription. Meanwhile, HVJ-E decreases S62 phosphorylation of c-Myc and promotes c-Myc protein degradation. Thus, HVJ-E-induced cell death of MM resulted from suppression of c-Myc by both destabilization of c-Myc protein and downregulation of c-Myc transcription. This study indicates that HVJ-E will be a promising tool for MM therapy. Impact Journals LLC 2016-04-29 /pmc/articles/PMC5094981/ /pubmed/27145280 http://dx.doi.org/10.18632/oncotarget.9105 Text en Copyright: © 2016 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jiang, Yingzhe
Saga, Kotaro
Miyamoto, Yasuhide
Kaneda, Yasufumi
Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title_full Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title_fullStr Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title_full_unstemmed Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title_short Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene
title_sort cytoplasmic calcium increase via fusion with inactivated sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-myc oncogene
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094981/
https://www.ncbi.nlm.nih.gov/pubmed/27145280
http://dx.doi.org/10.18632/oncotarget.9105
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