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

doi:10.3390/cancers11020177

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 journal › Article

2 Citations (Scopus)

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 language	English
Article number	177
Journal	Cancers
Volume	11
Issue number	2
DOIs	https://doi.org/10.3390/cancers11020177
Publication status	Published - Feb 2019

Keywords

Cancer stem cells
Combination therapy
Iron
Stemness

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3390/cancers11020177

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Katsura, Y., Ohara, T., Noma, K., Ninomiya, T., Kashima, H., Kato, T., Sato, H., Komoto, S., Narusaka, T., Tomono, Y., Xing, B., Chen, Y., Tazawa, H., Kagawa, S., Shirakawa, Y., Kasai, T., Seno, M., Matsukawa, A., & Fujiwara, T. (2019). A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness. Cancers, 11(2), [177]. https://doi.org/10.3390/cancers11020177

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, 02.2019.

Research output: Contribution to journal › Article

Katsura, Y, Ohara, T , Noma, K, Ninomiya, T, Kashima, H, Kato, T, Sato, H, Komoto, S, Narusaka, T, Tomono, Y, Xing, B, Chen, Y, Tazawa, H , Kagawa, S , Shirakawa, Y , Kasai, T , Seno, M , Matsukawa, A & Fujiwara, T 2019, 'A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness', Cancers, vol. 11, no. 2, 177. https://doi.org/10.3390/cancers11020177

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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