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The cytotoxic natural compound erianin binds to colchicine site of β-tubulin and overcomes taxane resistance.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2024 Sep; Vol. 150, pp. 107569. Date of Electronic Publication: 2024 Jun 17. - Publication Year :
- 2024
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Abstract
- Erianin, a natural compound derived from Dendrobium, has shown significant anticancer properties against a wide range of cancer cells. Despite the identification of multiple mechanisms of action for erianin, none of these mechanisms fully account for its broad-spectrum effect. In this study, we aimed to identify the cellular target and underlying mechanism responsible for the broad-spectrum antitumor effects of erianin. We found that erianin effectively inhibited tubulin polymerization in cancer cells and purified tubulin. Through competition binding assays and X-ray crystallography, it was revealed that erianin bound to the colchicine site of β-tubulin. Importantly, the X-ray crystal structure of the tubulin-erianin complex was solved, providing clear insight into the orientation and position of erianin in the colchicine-binding site. Erianin showed activity against paclitaxel-resistant cells, evidenced by G2/M cell cycle arrest, apoptosis-related PARP and Caspase-3 cleavage, and in vivo xenograft studies. The study concluded that erianin bound reversibly to the colchicine site of β-tubulin, inhibited tubulin polymerization, and displayed anticancer activity against paclitaxel-resistant cells, offering valuable insights for further exploration as potential anticancer agents.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Binding Sites
Animals
Structure-Activity Relationship
Molecular Structure
Dose-Response Relationship, Drug
Mice
Apoptosis drug effects
Taxoids pharmacology
Taxoids chemistry
Tubulin Modulators pharmacology
Tubulin Modulators chemistry
Crystallography, X-Ray
Bridged-Ring Compounds chemistry
Bridged-Ring Compounds pharmacology
Mice, Nude
Cell Line, Tumor
Biological Products chemistry
Biological Products pharmacology
Bibenzyls chemistry
Bibenzyls pharmacology
Phenol
Tubulin metabolism
Tubulin chemistry
Colchicine pharmacology
Colchicine chemistry
Colchicine metabolism
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents chemical synthesis
Drug Screening Assays, Antitumor
Drug Resistance, Neoplasm drug effects
Cell Proliferation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 150
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38905886
- Full Text :
- https://doi.org/10.1016/j.bioorg.2024.107569