ID 113047
Author
Kamihara, Yusuke Sapporo Medical University
Takada, Kohichi Sapporo Medical University
Sato, Tsutomu Sapporo Medical University
Kawano, Yutaka Sapporo Medical University
Murase, Kazuyuki Sapporo Medical University
Arihara, Yohei Sapporo Medical University
Kikuchi, Shohei Sapporo Medical University
Hayasaka, Naotaka Sapporo Medical University
Usami, Makoto Sapporo Medical University
Iyama, Satoshi Sapporo Medical University
Miyanishi, Koji Sapporo Medical University
Kobune, Masayoshi Sapporo Medical University
Kato, Junji Sapporo Medical University
Keywords
deferasirox
Pyk2
β-catenin
apoptosis
multiple myeloma
Content Type
Journal Article
Description
Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals, LLC
Volume
7
Issue
39
Start Page
64330
End Page
64341
Published Date
2016-09-02
Remark
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences