[Discovery of Streptospherins, Novel Cancer Stem Cell Inhibitors].

Authors

Hiroaki Ikeda

Published in

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. Volume 146. Issue 10. Pages 837-841.

Abstract

Targeting cancer stem cells (CSCs) is a promising strategy for preventing cancer progression and recurrence because of their high malignancy. To identify candidate CSC inhibitors, we established a new screening strategy using colorectal CSC spheres in a three-dimensional culture system. The obtained CSC spheres exhibited elevated expression of stemness markers and resistance to conventional anticancer agents. Using this system, we identified streptospherins A-F (1-6), isolated from Streptomyces sp. KUSC-240, as novel inhibitors of CSC sphere formation. Their planar structures were elucidated by high resolution electrospray ionization mass spectrometry (ESI-MS) and NMR analyses. The absolute configurations of 3-5 were proposed using spectroscopic analyses [J-based configuration (JBCA) analysis and ECD spectral analysis] together with chemical derivatization methods (modified Mosher's method and acetonide formation). A plausible biosynthetic pathway for compounds 3-5 was proposed based on the whole genome sequence analysis of the producing strain. Compounds 1-6 suppressed both CSC sphere formation and CSC proliferation, indicating the potential of streptospherins as promising seed compounds for CSC-targeted cancer chemotherapy.

PMID:
42816350
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.

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