Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Bruceantin inhibits the c-Myc/RL27A axis to suppress tumor progression in hepatocellular carcinoma.
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Islam Baitul, Adonira Saro, Xu Weiye, Chen Ceshi, Yu Haiyang, Huang Jufang
Аннотация
BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and is associated with a poor prognosis. Current treatment options for advanced HCC remain limited, highlighting the need for more effective and safer therapies.
PURPOSE: This study aimed to elucidate the anti-cancer efficacy and explore the molecular mechanism of Bruceantin (BCT) against HCC.
METHODS: We screened natural compounds using an extensive literature review and CCK-8 assays to identify novel therapeutic candidates. Using in vitro (HepG2.2.15 and Hep3B) and in vivo models, we assessed the BCT's effects through CCK-8, colony formation, wound-healing, flow cytometry, Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), qPCR, Western blot (WB), Luciferase reporter assay, and CETSA.
RESULTS: Bruceantin (BCT) significantly inhibited HCC cell proliferation and migration and induced apoptosis. In mouse xenograft models, it markedly suppressed tumor growth without observable toxicity. Transcriptomic profiling revealed that BCT broadly downregulated ribosomal protein genes, with RPL27A showing the most notable reduction. Further investigations demonstrated that RPL27A plays a crucial role in supporting HCC cell survival and inhibiting apoptosis, and its high expression is clinically associated with poor prognosis. Mechanistically, BCT decreased RPL27A expression by inhibiting c-Myc's transcriptional activity, thus preventing its capacity to activate RPL27A transcription. This disruption of the c-Myc/RPL27A axis contributes to BCT's antitumor effects.
CONCLUSION: This study reveals a new molecular mechanism underlying BCT's antitumor activity and supports its potential as a therapeutic agent for HCC.
PURPOSE: This study aimed to elucidate the anti-cancer efficacy and explore the molecular mechanism of Bruceantin (BCT) against HCC.
METHODS: We screened natural compounds using an extensive literature review and CCK-8 assays to identify novel therapeutic candidates. Using in vitro (HepG2.2.15 and Hep3B) and in vivo models, we assessed the BCT's effects through CCK-8, colony formation, wound-healing, flow cytometry, Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), qPCR, Western blot (WB), Luciferase reporter assay, and CETSA.
RESULTS: Bruceantin (BCT) significantly inhibited HCC cell proliferation and migration and induced apoptosis. In mouse xenograft models, it markedly suppressed tumor growth without observable toxicity. Transcriptomic profiling revealed that BCT broadly downregulated ribosomal protein genes, with RPL27A showing the most notable reduction. Further investigations demonstrated that RPL27A plays a crucial role in supporting HCC cell survival and inhibiting apoptosis, and its high expression is clinically associated with poor prognosis. Mechanistically, BCT decreased RPL27A expression by inhibiting c-Myc's transcriptional activity, thus preventing its capacity to activate RPL27A transcription. This disruption of the c-Myc/RPL27A axis contributes to BCT's antitumor effects.
CONCLUSION: This study reveals a new molecular mechanism underlying BCT's antitumor activity and supports its potential as a therapeutic agent for HCC.