TY - JOUR
T1 - A novel combination cancer therapy with iron chelator targeting cancer stem cells via suppressing stemness
AU - Katsura, Yuki
AU - Ohara, Toshiaki
AU - Noma, Kazuhiro
AU - Ninomiya, Takayuki
AU - Kashima, Hajime
AU - Kato, Takuya
AU - Sato, Hiroaki
AU - Komoto, Satoshi
AU - Narusaka, Toru
AU - Tomono, Yasuko
AU - Xing, Boyi
AU - Chen, Yuehua
AU - Tazawa, Hiroshi
AU - Kagawa, Shunsuke
AU - Shirakawa, Yasuhiro
AU - Kasai, Tomonari
AU - Seno, Masaharu
AU - Matsukawa, Akihiro
AU - Fujiwara, Toshiyoshi
N1 - Funding Information:
Funding: This work was supported by grants-in-aid from the Ministry of Education, Science, and Culture, Japan; and grants from the Ministry of Health and Welfare, Japan (18K08539).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - Combination therapy
KW - Iron
KW - Stemness
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U2 - 10.3390/cancers11020177
DO - 10.3390/cancers11020177
M3 - Article
AN - SCOPUS:85062388345
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 177
ER -
