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Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea 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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Autores principales: Li, Tsung-Ju, Lin, Ting-Wei, Wu, Shih-Pei, Chu, Hsin-Tung, Kuo, Yu-Hsuan, Chiou, Jeng-Fong, Lu, Long-Sheng, Chen, Chin-Chu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512555/
https://www.ncbi.nlm.nih.gov/pubmed/34641562
http://dx.doi.org/10.3390/molecules26196018
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author Li, Tsung-Ju
Lin, Ting-Wei
Wu, Shih-Pei
Chu, Hsin-Tung
Kuo, Yu-Hsuan
Chiou, Jeng-Fong
Lu, Long-Sheng
Chen, Chin-Chu
author_facet Li, Tsung-Ju
Lin, Ting-Wei
Wu, Shih-Pei
Chu, Hsin-Tung
Kuo, Yu-Hsuan
Chiou, Jeng-Fong
Lu, Long-Sheng
Chen, Chin-Chu
author_sort Li, Tsung-Ju
collection PubMed
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 Antrodia Cinnamomea 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 Antrodia cinnamomea mycelium (ACM) 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 pubmed-85125552021-10-14 Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound Li, Tsung-Ju Lin, Ting-Wei Wu, Shih-Pei Chu, Hsin-Tung Kuo, Yu-Hsuan Chiou, Jeng-Fong Lu, Long-Sheng Chen, Chin-Chu Molecules Article 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 Antrodia Cinnamomea 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 Antrodia cinnamomea mycelium (ACM) 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. MDPI 2021-10-04 /pmc/articles/PMC8512555/ /pubmed/34641562 http://dx.doi.org/10.3390/molecules26196018 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Tsung-Ju
Lin, Ting-Wei
Wu, Shih-Pei
Chu, Hsin-Tung
Kuo, Yu-Hsuan
Chiou, Jeng-Fong
Lu, Long-Sheng
Chen, Chin-Chu
Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title_full Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title_fullStr Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title_full_unstemmed Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title_short Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
title_sort patient-derived tumor chemosensitization of gkb202, an antrodia cinnamomea mycelium-derived bioactive compound
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512555/
https://www.ncbi.nlm.nih.gov/pubmed/34641562
http://dx.doi.org/10.3390/molecules26196018
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