A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness
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 nov...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/2/177 |
| _version_ | 1797711688821112832 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yuki Katsura |
| collection | DOAJ |
| description | 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 <i>Nanog</i>, <i>Oct3/4</i>, <i>Sox2</i>, <i>Klf4</i>, and <i>c-Myc</i>, 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. |
| first_indexed | 2024-03-12T07:10:45Z |
| format | Article |
| id | doaj.art-03d3be18b54b478e93137b150de1b6c1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:10:45Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-03d3be18b54b478e93137b150de1b6c12023-09-02T23:05:59ZengMDPI AGCancers2072-66942019-02-0111217710.3390/cancers11020177cancers11020177A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing StemnessYuki Katsura0Toshiaki Ohara1Kazuhiro Noma2Takayuki Ninomiya3Hajime Kashima4Takuya Kato5Hiroaki Sato6Satoshi Komoto7Toru Narusaka8Yasuko Tomono9Boyi Xing10Yuehua Chen11Hiroshi Tazawa12Shunsuke Kagawa13Yasuhiro Shirakawa14Tomonari Kasai15Masaharu Seno16Akihiro Matsukawa17Toshiyoshi Fujiwara18Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Shigei Medical Research Institute, Okayama 701-0202, JapanDepartment 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, JapanDepartment 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, JapanDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo 192-0914, JapanLaboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama 700-8530, JapanDepartment 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, JapanDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan <email>kyuki82@yahoo.co.jp</email> (Y.K.)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 <i>Nanog</i>, <i>Oct3/4</i>, <i>Sox2</i>, <i>Klf4</i>, and <i>c-Myc</i>, 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.https://www.mdpi.com/2072-6694/11/2/177cancer stem cellsstemnessironcombination therapy |
| spellingShingle | 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 A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness Cancers cancer stem cells stemness iron combination therapy |
| title | A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness |
| title_full | A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness |
| title_fullStr | A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness |
| title_full_unstemmed | A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness |
| title_short | A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness |
| title_sort | novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness |
| topic | cancer stem cells stemness iron combination therapy |
| url | https://www.mdpi.com/2072-6694/11/2/177 |
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