A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness
by
Yuki Katsura 1, Toshiaki Ohara 1,2,*
, Kazuhiro Noma 1, Takayuki Ninomiya 1, Hajime Kashima 1, Takuya Kato 1, Hiroaki Sato 1, Satoshi Komoto 1, Toru Narusaka 1, Yasuko Tomono 3, Boyi Xing 2, Yuehua Chen 2, Hiroshi Tazawa 1,4, Shunsuke Kagawa 1, Yasuhiro Shirakawa 1, Tomonari Kasai 5, Masaharu Seno 6, Akihiro Matsukawa 2 and Toshiyoshi Fujiwara 1
Yuki Katsura 1, Toshiaki Ohara 1,2,*, Kazuhiro Noma 1, Takayuki Ninomiya 1, Hajime Kashima 1, Takuya Kato 1, Hiroaki Sato 1, Satoshi Komoto 1, Toru Narusaka 1, Yasuko Tomono 3, Boyi Xing 2, Yuehua Chen 2, Hiroshi Tazawa 1,4, Shunsuke Kagawa 1, Yasuhiro Shirakawa 1, Tomonari Kasai 5, Masaharu Seno 6, Akihiro Matsukawa 2 and Toshiyoshi Fujiwara 1
1
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan [email protected] (Y.K.)
2
Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
3
Shigei Medical Research Institute, Okayama 701-0202, Japan
4
Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama 700-8558, Japan
5
School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo 192-0914, Japan
6
Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama 700-8530, Japan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(2), 177; https://doi.org/10.3390/cancers11020177
Received: 24 December 2018 / Revised: 28 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
(This article belongs to the Special Issue Advances in Cancer Stem Cell Research)
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.
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Keywords:
cancer stem cells; stemness; iron; combination therapy
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MDPI and ACS Style
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. A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness. Cancers 2019, 11, 177.
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