Oncotarget

Research Papers:

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

Yingzhe Jiang, Kotaro Saga, Yasuhide Miyamoto and Yasufumi Kaneda _

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Oncotarget. 2016; 7:36034-36048. https://doi.org/10.18632/oncotarget.9105

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Abstract

Yingzhe Jiang1, Kotaro Saga1, Yasuhide Miyamoto2, Yasufumi Kaneda1

1Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan

2Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

Correspondence to:

Yasufumi Kaneda, email: [email protected]

Keywords: HVJ-E, apoptosis, Ca2+, c-Myc, multiple myeloma

Received: October 26, 2015     Accepted: April 16, 2016     Published: April 29, 2016

ABSTRACT

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 Ca2+ 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 Ca2+ level of MMs by the induction of Ca2+ efflux from endoplasmic reticulum but not influx from extracellular region. The elevation of the Ca2+ 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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