{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:29:09Z","timestamp":1792225749861,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Agriculture, Food, and Rural Affairs (MAFRA)","award":["120025-02-2-CG000"],"award-info":[{"award-number":["120025-02-2-CG000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Cachexia, which is characterised by the wasting of fat and skeletal muscles, is the most common risk factor for increased mortality rates among patients with advanced lung cancer. PTHLH (parathyroid hormone-like hormone) is reported to be involved in the pathogenesis of cancer cachexia. However, the molecular mechanisms underlying the regulation of PTHLH expression and the inhibitors of PTHLH have not yet been identified. The PTHLH mRNA levels were measured using quantitative real-time polymerase chain reaction, while the PTHrP (parathyroid hormone-related protein) expression levels were measured using Western blotting and enzyme-linked immunosorbent assay. The interaction between TCF4 (Transcription Factor 4) and TWIST1 and the binding of the TCF4\u2013TWIST1 complex to the PTHLH promoter were analysed using co-immunoprecipitation and chromatin immunoprecipitation. The results of the mammalian two-hybrid luciferase assay revealed that emodin inhibited TCF4\u2013TWIST1 interaction. The effects of Polygonum cuspidatum extract (Pc-Ex), which contains emodin, on cachexia were investigated in vivo using A549 tumour-bearing mice. Ectopic expression of TCF4 upregulated PTHLH expression. Conversely, TCF4 knockdown downregulated PTHLH expression in lung cancer cells. The expression of PTHLH was upregulated in cells ectopically co-expressing TCF4 and TWIST1 when compared with that in cells expressing TCF4 or TWIST1 alone. Emodin inhibited the interaction between TCF4 and TWIST1 and consequently suppressed the TCF4\/TWIST1 complex-induced upregulated mRNA and protein levels of PTHLH and PTHrP. Meanwhile, emodin-containing Pc-Ex significantly alleviated skeletal muscle atrophy and downregulated fat browning-related genes in A549 tumour-bearing mice. Emodin-containing Pc-Ex exerted therapeutic effects on lung cancer-associated cachexia by inhibiting TCF4\/TWIST1 complex-induced PTHrP expression.<\/jats:p>","DOI":"10.3390\/nu14071508","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T06:01:34Z","timestamp":1649138494000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polygonum cuspidatum Extract (Pc-Ex) Containing Emodin Suppresses Lung Cancer-Induced Cachexia by Suppressing TCF4\/TWIST1 Complex-Induced PTHrP Expression"],"prefix":"10.3390","volume":"14","author":[{"given":"Xue-Quan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"},{"name":"Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Seon","family":"Kim","sequence":"additional","affiliation":[{"name":"Jung-Ang Microbe Research Institute (JM), 398, Jikji-daero, Heungdeok-gu, Cheongju 28576, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Mi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Jin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"},{"name":"Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Jong","family":"Yim","sequence":"additional","affiliation":[{"name":"Jung-Ang Microbe Research Institute (JM), 398, Jikji-daero, Heungdeok-gu, Cheongju 28576, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Korea Institute of Knowledge Service, 20 Wolpyeongsaetteum-ro, Seo-gu, Daejeon 35226, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"},{"name":"Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, 268 Chungwon-daero, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/1759-7714.12910","article-title":"Updates on the pathogenesis of advanced lung cancer-induced cachexia","volume":"10","author":"Zhu","year":"2019","journal-title":"Thorac. 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