دورية أكاديمية
Streptonigrin Mitigates Lung Cancer-induced Cachexia by Suppressing TCF4/TWIST1-induced PTHLH Expression.
| العنوان: | Streptonigrin Mitigates Lung Cancer-induced Cachexia by Suppressing TCF4/TWIST1-induced PTHLH Expression. |
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| المؤلفون: | Fang XQ; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Lee S; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Kim YS; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea.; Jung-Ang Microbe Research Institute (JM), Heungdeok-gu, Cheongju, Republic of Korea., Han GE; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea., Lim CH; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Lim JH; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea; jhlim@kku.ac.kr.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea.; Center for Metabolic Diseases, Konkuk University, Chungju, Republic of Korea. |
| المصدر: | Anticancer research [Anticancer Res] 2023 Mar; Vol. 43 (3), pp. 1149-1157. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: International Institute of Anticancer Research Country of Publication: Greece NLM ID: 8102988 Publication Model: Print Cited Medium: Internet ISSN: 1791-7530 (Electronic) Linking ISSN: 02507005 NLM ISO Abbreviation: Anticancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Attiki, Greece : International Institute of Anticancer Research Original Publication: Athens, Greece : Potamitis Press |
| مواضيع طبية MeSH: | Cachexia*/drug therapy , Cachexia*/etiology , Lung Neoplasms*/complications , Lung Neoplasms*/drug therapy, Animals ; Mice ; Adipose Tissue ; Adiposity ; Mammals ; Streptonigrin |
| مستخلص: | Background/aim: Cachexia - a wasting disorder of adipose and skeletal muscle tissue - is the most common driver of poor prognosis in patients with advanced lung cancer. Parathyroid hormone-like hormone (PTHLH) is potentially a critical factor in cancer-associated cachexia. We previously showed that streptonigrin - an aminoquinone with antitumor effects - inhibited the interaction between TCF4 and TWIST1. This study aimed to determine the anti-cachectic performance of streptonigrin in lung cancer. Materials and Methods: We assessed the effect of streptonigrin on the interaction of TCF4 and TWIST1 using co-immunoprecipitation and a mammalian-two hybrid luciferase assay, which was confirmed by an in vitro GST pull-down assay using recombinant bHLH domain-containing TCF4 and TWIST1. We assessed the anti-cachectic effect of streptonigrin in vivo using an LLC1 cell-induced tumour-bearing mouse model. Changes in the degree of skeletal muscle and adipose tissue wasting were determined by measuring the weights of gastrocnemius and epidydimal white adipose tissue. Results: Streptonigrin was found to inhibit the interaction of TCF4 with TWIST1 in a dose-dependent manner. The in vitro GST pull-down assay revealed that streptonigrin directly inhibited the interaction between TCF4 and TWIST1. The expression of PTHLH mRNA, which is transcriptionally regulated by the TCF4/TWIST1 complex in response to TGF-β1 signalling, was decreased in streptonigrin-treated lung cancer cells. Streptonigrin significantly decreased the expression of proteolysis-related genes in skeletal muscle and browning-related genes in white adipose tissues of LLC1-induced tumour-bearing mice. Conclusion: Streptonigrin exerts potent therapeutic effects on lung cancer-induced cachexia by suppressing TCF4/TWIST1-mediated PTHLH expression. (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) |
| فهرسة مساهمة: | Keywords: Lung cancer; PTHLH; TCF4; TWIST1; cachexia; streptonigrin |
| المشرفين على المادة: | 261Q3JB310 (Streptonigrin) 0 (Tcf4 protein, mouse) 136253-27-5 (Twist1 protein, mouse) 0 (Pthlh protein, mouse) |
| تواريخ الأحداث: | Date Created: 20230228 Date Completed: 20240124 Latest Revision: 20240124 |
| رمز التحديث: | 20240124 |
| DOI: | 10.21873/anticanres.16260 |
| PMID: | 36854496 |
| قاعدة البيانات: | MEDLINE |
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