Chetomin, a Hsp90/HIF1α pathway inhibitor, effectively targets lung cancer stem cells and non-stem cells
Open accessAbstract
Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse and resistance and are consequently considered promising drug targets. We report that chetomin, an active component of Chaetomium globosum, blocks heat shock protein 90/hypoxia-inducible factor 1 alpha (Hsp90/HIF1α) pathway activity. Chetomin also attenuated sphere-forming, a stem cell-like characteristic, of NSCLC CSCs (at ~ nM range) and the proliferation of non-CSCs NSCLC cultures and chemoresistant sublines (at ~ μM range). At these concentrations, chetomin exerted a marginal influence on noncancerous cells originating from several organs. Chetomin markedly decreased in vivo tumor formation in a spontaneous KrasLA1 lung cancer model, flank xenograft models, and a tumor propagation flank implanted model at doses that did not produce an observable toxicity to the animals. Chetomin blocked Hsp90/HIF1α pathway activity via inhibiting the Hsp90-HIF1α binding interaction without affecting Hsp90 or Hsp70 protein levels. This study advocates chetomin as a Hsp90/HIF1α pathway inhibitor and a potent, nontoxic NSCLC CSC-targeting molecule.
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Chetomin may also interfere with HSP90 binding to HIF-1α, thereby reducing HIF-1α accumulation independently of p300 disruption.
“Additional studies suggest that chetomin may also interfere with HSP90 binding to HIF-1α, thereby reducing HIF-1α accumulation independently of p300 disruption [400].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [400]
The Hsp90/HIF1α activity section reports that chetomin reduced both Hsp90–HIF1α binding and HIF1α protein expression. But the Discussion suggests that chetomin disrupts Hsp90 binding indirectly through p300, contrary to the claim that it does so independently of p300 disruption. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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- Authors
- Min, S., Wang, X., Du, Q., Gong, H., Yang, Y., Wang, T., Wu, N., Liu, X., Li, W., Zhao, C., Shen, Y., Chen, Y., & Wang, X.
- Affiliations
- Bengbu Medical College (CN)
- Department of Medical Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China
- Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease; Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China
- Corresponding author
- Wang, Xiaojing
- Venue
- Cancer Biology & Therapy
- Publisher
- Informa UK Limited
- Published
- 2020-06-03
- Volume
- 21
- Issue
- 8
- Pages
- 698-708
- ISSN
- 1538-4047 (ISSN-L)
- 1555-8576
- PMC
- PMC7515479
- OpenAlex
- W3031148234
- Cited by
- 28
- References
- 44
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 12 · 2021: 1
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Biology & Therapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81772493)
- Science and Technology Program of Anhui Province (2017070503B037, YDZX20183400002554)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- chetomin, non-small cell lung cancer, cancer stem cells, chemoresistance, tumor recurrence, Chaetomium globosum, sphere formation, xenograft tumor growth, anticancer natural products
- MeSH terms
- Animals, Disease Models, Animal, Disulfides, Humans, Lung Neoplasms, Mycotoxins, Neoplastic Stem Cells, HSP90 Heat-Shock Proteins, Indole Alkaloids, Cell Line, Tumor, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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