A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness

Yuki Katsura, Toshiaki Ohara, Kazuhiro Noma, Takayuki Ninomiya, Hajime Kashima, Takuya Kato, Hiroaki Sato, Satoshi Komoto, Toru Narusaka, Yasuko Tomono, Boyi Xing, Yuehua Chen, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

Abstract

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

Original languageEnglish
Article number177
JournalCancers
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Neoplastic Stem Cells
Chelating Agents
Iron
Neoplasms
Stem Cells
Therapeutics
Induced Pluripotent Stem Cells
Cell- and Tissue-Based Therapy
Cisplatin
Carcinogenesis
Maintenance
Gene Expression
Drug Therapy
Cell Line
Genes

Keywords

  • Cancer stem cells
  • Combination therapy
  • Iron
  • Stemness

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness. / Katsura, Yuki; Ohara, Toshiaki; Noma, Kazuhiro; Ninomiya, Takayuki; Kashima, Hajime; Kato, Takuya; Sato, Hiroaki; Komoto, Satoshi; Narusaka, Toru; Tomono, Yasuko; Xing, Boyi; Chen, Yuehua; Tazawa, Hiroshi; Kagawa, Shunsuke; Shirakawa, Yasuhiro; Kasai, Tomonari; Seno, Masaharu; Matsukawa, Akihiro; Fujiwara, Toshiyoshi.

In: Cancers, Vol. 11, No. 2, 177, 01.02.2019.

Research output: Contribution to journalArticle

Katsura, Yuki ; Ohara, Toshiaki ; Noma, Kazuhiro ; Ninomiya, Takayuki ; Kashima, Hajime ; Kato, Takuya ; Sato, Hiroaki ; Komoto, Satoshi ; Narusaka, Toru ; Tomono, Yasuko ; Xing, Boyi ; Chen, Yuehua ; Tazawa, Hiroshi ; Kagawa, Shunsuke ; Shirakawa, Yasuhiro ; Kasai, Tomonari ; Seno, Masaharu ; Matsukawa, Akihiro ; Fujiwara, Toshiyoshi. / A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness. In: Cancers. 2019 ; Vol. 11, No. 2.
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