Effective impairment of myeloma cells and their progenitors by hyperthermia

Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Kenichi Aihara, Mariko Ikuo, Kohji ItohKoichiro Hayashi, Michihiro Nakamura, Masahiro Abe

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drugresistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated "side population" fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs.

Original languageEnglish
Pages (from-to)10307-10316
Number of pages10
Issue number12
Publication statusPublished - 2018
Externally publishedYes


  • Bortezomib
  • Hyperthermia
  • Pim-2
  • Plasmacytoma
  • Side population

ASJC Scopus subject areas

  • Oncology


Dive into the research topics of 'Effective impairment of myeloma cells and their progenitors by hyperthermia'. Together they form a unique fingerprint.

Cite this