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Honokiol‐Magnolol‐Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti‐PD‐1 Immunotherapy in Colorectal Cancer by Triggering GSDME‐Dependent Pyroptosis
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Honokiol‐Magnolol‐Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti‐PD‐1 Immunotherapy in Colorectal Cancer by Triggering GSDME‐Dependent Pyroptosis
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Honokiol‐Magnolol‐Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti‐PD‐1 Immunotherapy in Colorectal Cancer by Triggering GSDME‐Dependent Pyroptosis
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Journal Article
Honokiol‐Magnolol‐Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti‐PD‐1 Immunotherapy in Colorectal Cancer by Triggering GSDME‐Dependent Pyroptosis
2025
Overview
Significant progress is made in the treatment of metastatic colorectal cancer (mCRC) patients, however, therapeutic options remain limited for patients with mCRC. In recent years, traditional Chinese medicine (TCM) has gained significant attention. Among these, Huangqin Houpo decoction has demonstrated efficacy in mCRC treatment. Despite its promise, the active ingredients and mechanisms underlying its anticancer effects remain unclear. Using integrative pharmacological approaches, six compounds are identified as the primary active ingredients in Huangqin Houpo decoction. Among them, honokiol (H), magnolol (M), and baicalin (B) are found to exhibit a synergistic anticancer effect on CRC. The HMB combination significantly outperforms mono‐ or bi‐agent treatments in reducing tumor growth. Furthermore, the anticancer efficacy of the HMB combination surpasses that of medium‐ and high‐dose Huangqin Houpo decoction and the FOLFOX regimen. Notably, HMB is comparable in efficacy to the FOLFIRI regimen. Most importantly, HMB is shown to enhance the sensitivity of CRC cells to anti‐PD‐1 immunotherapy in vivo. Mechanistic studies reveal that the HMB combination exerts its synergistic anticancer effects and enhances anti‐PD‐1 immunotherapy by inducing GSDME‐dependent pyroptosis. Our study will hopefully provide a potential therapeutic strategy for mCRC patients in the future. [Correction added on 25 February 2025, after first online publication: FOLFOIRI is changed to FOLFIRI.] In this study, Honokiol (H)‐magnolol (M)‐baicalin (B) is identified as the primary active ingredients of Huangqin Houpo decoction. The HMB combination not only possesses potent synergistic anticancer activity, but also enhances the effectiveness of anti‐PD‐1 immunotherapy by inducing GSDME‐dependent pyroptosis in CRC cells.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Animals
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ Biphenyl Compounds - pharmacology
/ Biphenyl Compounds - therapeutic use
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - metabolism
/ Datasets
/ Drugs
/ Flavonoids - therapeutic use
/ GSDME
/ Humans
/ metastatic colorectal cancer
/ Mice
/ Phenols
/ Programmed Cell Death 1 Receptor - antagonists & inhibitors
/ Traditional Chinese medicine
/ Tumors
