Development of a traditional Chinese medicine‐based agent for the treatment of cancer cachexia

Background Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. Methods We developed an integrated, multi‐tiered strategy involving both in vitro and in vivo muscle atrophy platforms to ident...

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Published in:Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2022-08, Vol.13 (4), p.2073-2087
Main Authors: Wu, Kun‐Chang, Chu, Po‐Chen, Cheng, Yu‐Jung, Li, Chia‐Ing, Tian, Jingkui, Wu, Hsing‐Yu, Wu, Szu‐Hsien, Lai, Yi‐Chun, Kao, Hsiang‐Han, Hsu, Ao‐Lin, Lin, Hsiang‐Wen, Lin, Chih‐Hsueh
Format: Article
Language:English
Subjects:
Age
Atrophy
C2C12 cell model
Cachexia
Caenorhabditis elegans model
Chinese medicine
Chronic illnesses
Colorectal cancer
C‐26 tumour‐bearing model
Gene expression
Herbal medicine
Muscle atrophy
Nematodes
Original
Sarcopenia
Traditional Chinese medicine
Worms
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Summary:Background Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. Methods We developed an integrated, multi‐tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)‐based anti‐cachectic agents. In the initial screening, we used inflammatory cytokine‐induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age‐related reduction of mobility and contractility, followed by the C‐26 colon adenocarcinoma mouse model of cachexia to confirm the anti‐muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL‐6). Transcriptome analysis, quantitative real‐time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour‐induced muscle atrophy. Results Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis‐à‐vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age‐associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P 
ISSN:2190-5991
2190-6009
DOI:10.1002/jcsm.13028