Identification of Bruceine A as a novel HSP90AB1 inhibitor for suppressing hepatocellular carcinoma growth
Related Experiment Video
Updated: May 1, 2026
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Weijun Peng1, Dazun Shi2, Die Xu3
1Department of Integrated Traditional Chinese & Western Medicine, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Academician Workstation, Changsha Medical University, Changsha 410219, China.
Introduction:
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic options available. Natural compounds, such as Bruceine A (BRA), derived from Brucea javanica, have emerged as promising anticancer agents. However, the underlying mechanisms of action in HCC remain largely unexplored.
Objectives:
This study aims to identify the molecular target of BRA and elucidate its anticancer effects.
Methods:
Patient-derived organoids (PDOs) and xenograft (PDX) models were employed to assess the anticancer activity of BRA. Chemical proteomics and binding assays, including MST, SPR, and CETSA, facilitated the identification of heat shock protein 90α family class B member 1 (HSP90AB1) as the primary target of BRA, with SER-108 identified as the critical binding site. HSP90AB1 knockdown further confirmed its pivotal role in BRA-mediated anti-HCC effects. Additionally, TMT-based proteomics was applied to investigate the downstream chaperones of HSP90AB1.
Results:
BRA significantly suppressed HCC proliferation and induced apoptosis. Molecular analyses revealed HSP90AB1 as the key target, with SER-108 as the critical binding site. Proteomic analysis identified downstream HSP90AB1 partner proteins, including PIK3CG, EGFR, and KDM5C, as contributors to BRA's inhibitory effects on HCC progression.
Conclusion:
This study establishes HSP90AB1 as the primary target of BRA, which exerts its anti-HCC effects through modulation of downstream chaperones PIK3CG, EGFR, and KDM5C. These findings highlight the therapeutic potential of BRA in HCC and suggest that HSP90AB1 represents a promising target for future drug development.
Insights
Bruceine A (BRA) targets heat shock protein 90α family class B member 1 (HSP90AB1) to inhibit hepatocellular carcinoma (HCC) growth. This natural compound shows promise for HCC treatment by modulating key downstream proteins.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) is a major global cancer burden with limited treatment options.
- Natural compounds like Bruceine A (BRA) show potential, but their mechanisms in HCC are unclear.
Purpose of the Study:
- Identify the molecular target of BRA in HCC.
- Elucidate the anticancer mechanisms of BRA.
Main Methods:
- Utilized patient-derived organoids (PDOs) and xenograft (PDX) models to test BRA's efficacy.
- Employed chemical proteomics and binding assays (MST, SPR, CETSA) to identify BRA's target.
- Performed HSP90AB1 knockdown and TMT-based proteomics to analyze downstream effects.
Main Results:
- BRA significantly reduced HCC proliferation and induced apoptosis.
- Identified heat shock protein 90α family class B member 1 (HSP90AB1) as the primary target, binding at SER-108.
- Proteomics revealed downstream targets PIK3CG, EGFR, and KDM5C involved in BRA's anti-HCC action.
Conclusions:
- HSP90AB1 is the key molecular target of BRA in HCC.
- BRA exerts anti-HCC effects by modulating HSP90AB1 and its downstream chaperones (PIK3CG, EGFR, KDM5C).
- BRA and targeting HSP90AB1 show therapeutic potential for HCC treatment.
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