Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficie...

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Main Authors: Tsung-Ju Li, Ting-Wei Lin, Shih-Pei Wu, Hsin-Tung Chu, Yu-Hsuan Kuo, Jeng-Fong Chiou, Long-Sheng Lu, Chin-Chu Chen
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/19/6018
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author Tsung-Ju Li
Ting-Wei Lin
Shih-Pei Wu
Hsin-Tung Chu
Yu-Hsuan Kuo
Jeng-Fong Chiou
Long-Sheng Lu
Chin-Chu Chen
author_facet Tsung-Ju Li
Ting-Wei Lin
Shih-Pei Wu
Hsin-Tung Chu
Yu-Hsuan Kuo
Jeng-Fong Chiou
Long-Sheng Lu
Chin-Chu Chen
author_sort Tsung-Ju Li
collection DOAJ
description Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test <i>Antrodia Cinnamomea</i> mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of <i>Antrodia cinnamomea</i> mycelium (<i>ACM</i>) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.
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spelling doaj.art-edf5e642b2ca47febd56bf887f48a4892023-11-22T16:36:06ZengMDPI AGMolecules1420-30492021-10-012619601810.3390/molecules26196018Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive CompoundTsung-Ju Li0Ting-Wei Lin1Shih-Pei Wu2Hsin-Tung Chu3Yu-Hsuan Kuo4Jeng-Fong Chiou5Long-Sheng Lu6Chin-Chu Chen7Biotech Research Institute, Grape King Bio, Taoyuan 32542, TaiwanBiotech Research Institute, Grape King Bio, Taoyuan 32542, TaiwanCancerFree Biotech Ltd., Taipei City 106, TaiwanBiotech Research Institute, Grape King Bio, Taoyuan 32542, TaiwanBiotech Research Institute, Grape King Bio, Taoyuan 32542, TaiwanDepartment of Radiation Oncology, Taipei Medical University Hospital, Taipei City 110, TaiwanDepartment of Radiation Oncology, Taipei Medical University Hospital, Taipei City 110, TaiwanBiotech Research Institute, Grape King Bio, Taoyuan 32542, TaiwanOral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test <i>Antrodia Cinnamomea</i> mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of <i>Antrodia cinnamomea</i> mycelium (<i>ACM</i>) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.https://www.mdpi.com/1420-3049/26/19/6018<i>Antrodia Cinnamomea</i> myceliumACMcirculating tumor cellspatient-derived organoid5-FU
spellingShingle Tsung-Ju Li
Ting-Wei Lin
Shih-Pei Wu
Hsin-Tung Chu
Yu-Hsuan Kuo
Jeng-Fong Chiou
Long-Sheng Lu
Chin-Chu Chen
Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
Molecules
<i>Antrodia Cinnamomea</i> mycelium
ACM
circulating tumor cells
patient-derived organoid
5-FU
title Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
title_full Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
title_fullStr Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
title_full_unstemmed Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
title_short Patient-Derived Tumor Chemosensitization of GKB202, an <i>Antrodia Cinnamomea</i> Mycelium-Derived Bioactive Compound
title_sort patient derived tumor chemosensitization of gkb202 an i antrodia cinnamomea i mycelium derived bioactive compound
topic <i>Antrodia Cinnamomea</i> mycelium
ACM
circulating tumor cells
patient-derived organoid
5-FU
url https://www.mdpi.com/1420-3049/26/19/6018
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