Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Neurology, Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
J Antibiot (Tokyo). 2022 Dec;75(12):671-678. doi: 10.1038/s41429-022-00571-1. Epub 2022 Oct 8.
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.
针对并根除癌症干细胞（CSC），也称为肿瘤起始细胞，是预防癌症进展和复发的有前途的策略。为了鉴定针对 CSC 的候选化合物，我们使用结直肠 CSC 球体和非 CSC 球体在三维（3D）培养系统中建立了一种新的筛选策略。通过使用我们的系统和内部微生物代谢产物文库进行化学筛选，我们鉴定了聚醚阳离子载体离子，它们选择性地抑制 CSC 球体形成，而 CSC 球体对常规抗癌药物具有抗性。其中一种命中化合物，最具选择性和有效的微生物代谢产物 lenoremycin，通过诱导活性氧产生来减少 CSC 群体。这项研究表明，我们新建立的筛选系统可用于发现选择性消除 CSC 的药物。
