Related Experiment Video
Updated: Aug 26, 2025
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Identification of the polyether ionophore lenoremycin through a new screening strategy for targeting cancer stem
Hiroaki Ikeda1, Misato Kawami1, Masaya Imoto2
1Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
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.
Insights
Researchers developed a novel screening method to find compounds that target cancer stem cells (CSCs). They discovered lenoremycin, a microbial metabolite, effectively eliminates CSCs by inducing reactive oxygen species.
Area of Science:
- Oncology
- Microbiology
- Drug Discovery
Background:
- Cancer stem cells (CSCs) are crucial for tumor progression and recurrence.
- Targeting CSCs is a promising strategy for effective cancer treatment.
- Conventional therapies often fail to eradicate CSCs, leading to relapse.
Purpose of the Study:
- To establish a novel screening system for identifying CSC-targeting compounds.
- To discover novel agents that selectively inhibit or eliminate CSCs.
- To evaluate the efficacy of identified compounds against colorectal CSCs.
Main Methods:
- Development of a 3D culture system with colorectal CSC spheres and non-CSC spheres.
- Chemical screening of an in-house microbial metabolite library.
- Assessment of compound selectivity and efficacy in inhibiting CSC sphere formation.
- Evaluation of lenoremycin's mechanism of action, including reactive oxygen species induction.
Main Results:
- A new screening system successfully identified compounds targeting CSCs.
- Polyether cation ionophores selectively inhibited CSC sphere formation.
- Lenoremycin, a potent microbial metabolite, demonstrated high selectivity and efficacy.
- Lenoremycin reduced CSC populations by inducing reactive oxygen species.
Conclusions:
- The established 3D screening system is effective for discovering CSC-selective agents.
- Lenoremycin is a promising candidate for targeting and eradicating cancer stem cells.
- This approach offers a new strategy for developing more effective cancer therapies.
More Related Videos
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
10:28Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
Published on: January 10, 2018