دورية أكاديمية
A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.
| العنوان: | A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo. |
|---|---|
| المؤلفون: | Li Q; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China., Niu JQ; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China., Jia JH; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China., Xu W; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China., Bai M; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China., Yao GD; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address: guodong_yao@126.com., Song SJ; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2024 Feb; Vol. 143, pp. 107007. Date of Electronic Publication: 2023 Nov 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| مواضيع طبية MeSH: | Carcinoma, Hepatocellular*/pathology , Liver Neoplasms*/pathology , Sesquiterpenes, Germacrane*, Humans ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors |
| مستخلص: | Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: EGFR; Elephantopus tomentosus; Hepatocellular carcinoma; Highly oxidized germacranolides |
| المشرفين على المادة: | 0 (germacranolide) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (EGFR protein, human) 0 (Sesquiterpenes, Germacrane) |
| تواريخ الأحداث: | Date Created: 20231201 Date Completed: 20240124 Latest Revision: 20240124 |
| رمز التحديث: | 20240124 |
| DOI: | 10.1016/j.bioorg.2023.107007 |
| PMID: | 38039928 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
|---|---|
| DOI: | 10.1016/j.bioorg.2023.107007 |