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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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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. |
format | Online Article Text |
id | pubmed-5094981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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