TY - JOUR
T1 - High-throughput screening identifies artesunate as selective inhibitor of cancer stemness
T2 - Involvement of mitochondrial metabolism
AU - Subedi, Amit
AU - Futamura, Yushi
AU - Nishi, Mayuko
AU - Ryo, Akihide
AU - Watanabe, Nobumoto
AU - Osada, Hiroyuki
N1 - Funding Information:
We thank members of RIKEN NPDepo for providing chemical libraries, and Noriko Ikawa (Yokohama City University School of Medicine) for assistance in drug screening. AS is grateful to RIKEN International Program Associate Fellowship. This research is partially supported by the research grant from MEXT and Japan Agency for Medical Research and Development .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/2
Y1 - 2016/9/2
N2 - Cancer stem cells (CSCs) have robust systems to maintain cancer stemness and drug resistance. Thus, targeting such robust systems instead of focusing on individual signaling pathways should be the approach allowing the identification of selective CSC inhibitors. Here, we used the alkaline phosphatase (ALP) assay to identify inhibitors for cancer stemness in induced cancer stem-like (iCSCL) cells. We screened several compounds from natural product chemical library and evaluated hit compounds for their efficacy on cancer stemness in iCSCL tumorspheres. We identified artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells, indicating an essential role of mitochondrial metabolism in cancer stemness.
AB - Cancer stem cells (CSCs) have robust systems to maintain cancer stemness and drug resistance. Thus, targeting such robust systems instead of focusing on individual signaling pathways should be the approach allowing the identification of selective CSC inhibitors. Here, we used the alkaline phosphatase (ALP) assay to identify inhibitors for cancer stemness in induced cancer stem-like (iCSCL) cells. We screened several compounds from natural product chemical library and evaluated hit compounds for their efficacy on cancer stemness in iCSCL tumorspheres. We identified artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells, indicating an essential role of mitochondrial metabolism in cancer stemness.
KW - Artesunate
KW - CSCs
KW - High-throughput screening
KW - Mitochondrial metabolism
KW - Tumorspheres
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U2 - 10.1016/j.bbrc.2016.06.128
DO - 10.1016/j.bbrc.2016.06.128
M3 - Article
C2 - 27363336
AN - SCOPUS:84979701636
SN - 0006-291X
VL - 477
SP - 737
EP - 742
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -