Streptospherin A, a New Cancer Stem Cell Inhibitor, Produced by Streptomyces sp. KUSC-240

Hiroaki Ikeda; Ami Mimura; Saki Makita; Kayo Funayama; Morihiro Shibasaki; Taiki Suo; Saya Yoshida; Takefumi Kuranaga; Kazutoshi Shindo; Kazuo Furihata; Masaya Imoto; Hideaki Kakeya

doi:10.1248/cpb.c25-00097

Note

Streptospherin A, a New Cancer Stem Cell Inhibitor, Produced by Streptomyces sp. KUSC-240

Hiroaki Ikeda, Ami Mimura, Saki Makita, Kayo Funayama, Morihiro Shibasaki, Taiki Suo, Saya Yoshida, Takefumi Kuranaga, Kazutoshi Shindo, Kazuo Furihata, Masaya Imoto, Hideaki Kakeya

Author information

Hiroaki Ikeda
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Ami Mimura
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Saki Makita
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3–14–1 Hiyoshi, Kohoku-ku, Yokohama 223–8522, Japan
Kayo Funayama
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3–14–1 Hiyoshi, Kohoku-ku, Yokohama 223–8522, Japan
Morihiro Shibasaki
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Taiki Suo
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Saya Yoshida
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Takefumi Kuranaga
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan
Kazutoshi Shindo
Department of Food and Nutrition, Japan Women’s University, 2–8–1 Mejirodai, Bunkyo-ku, Tokyo 112–8681, Japan
Kazuo Furihata
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan
Masaya Imoto
Department of Neurology, Division of Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421, Japan
Hideaki Kakeya Corresponding author
Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-machi, Sakyo-ku, Kyoto 606–8501, Japan

Keywords: cancer stem cell, natural product, structural determination, anticancer, Streptomyces sp.

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Supplementary material

2025 Volume 73 Issue 5 Pages 445-448

DOI https://doi.org/10.1248/cpb.c25-00097

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Abstract

Cancer stem cells (CSCs) are a major cause of tumor recurrence; therefore, using CSC inhibitors is a potential strategy for cancer chemotherapy. We used our previously reported screening system that targets CSCs to identify a new scarce compound, streptospherin A (1), isolated from Streptomyces sp. KUSC-240. The planar structure of 1 was determined by high-resolution-MS (HR-MS) and NMR analysis. Nuclear Overhauser effect spectroscopy correlation and J-resolved heteronuclear multiple bond connectivity analysis revealed the partial relative configuration on the tetrahydropyran ring. Streptospherin A (1) inhibited CSC sphere formation and suppressed the growth of CSCs. These results suggest that streptospherin A (1) is a potential anticancer agent that may target CSCs.

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