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  3. Identification of the polyether ionophore lenoremycin through a new screening strategy for targeting cancer stem cells

Identification of the polyether ionophore lenoremycin through a new screening strategy for targeting cancer stem cells

  • J Antibiot (Tokyo). 2022 Dec;75(12):671-678. doi: 10.1038/s41429-022-00571-1.
Hiroaki Ikeda 1,  Misato Kawami 1,  Masaya Imoto 2,  Hideaki Kakeya 3
Affiliations

Affiliations

  • 1 Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • 2 Department of Neurology, Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
  • 3 Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan. scseigyo-hisyo@pharm.kyoto-u.ac.jp.
PMID: 36207416 DOI: 10.1038/s41429-022-00571-1
Abstract

Targeting and eradicating Cancer Stem Cells (CSCs), also termed tumor-initiating cells, are promising strategies for preventing Cancer progression and recurrence. To identify candidate compounds targeting CSCs, we established a new screening strategy with colorectal CSC spheres and non-CSC spheres in three-dimensional (3D) culture system. Through chemical screening using our system with in-house microbial metabolite library, we identified polyether cation ionophores that selectively inhibited CSC sphere formation, whereas CSC spheres were resistant to conventional Anticancer agents. One of the hit compounds, the most selective and effective microbial metabolite lenoremycin, decreased CSC populations via inducing Reactive Oxygen Species production. This study demonstrated that our newly established screening system is useful for discovering agents that selectively eliminate CSCs.

Keywords

Cancer stem cells; Polyether ionophore; Reactive oxygen species; Screening.

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