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Solanum torvum induces ferroptosis to suppress hepatocellular carcinoma.
Lai, Hsiang-Chun; Weng, Jui-Chun; Huang, Hui-Chi; Ho, Jin-Xuan; Kuo, Chao-Lin; Cheng, Ju-Chien; Huang, Sheng-Teng.
Afiliación
  • Lai HC; Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Weng JC; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
  • Huang HC; School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Ho JX; Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
  • Kuo CL; Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
  • Cheng JC; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan. Electronic address: jccheng@mail.cmu.edu.tw.
  • Huang ST; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. E
J Ethnopharmacol ; 335: 118670, 2024 Dec 05.
Article en En | MEDLINE | ID: mdl-39117020
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Solanum torvum Sw. (ST) is used to clear heat toxins, promote blood circulation, and alleviate blood stasis. Therefore, this plant has traditionally been used as an ethnomedicine for common cold, chronic gastritis, and tumors. AIM OF THE STUDY This study aimed to elucidate the mechanism by which ST induces ferroptosis in hepatocellular carcinoma (HCC), the combination effect with lenvatinib, and the impact on lenvatinib-resistant cells. MATERIALS AND

METHODS:

Cell viability assays were performed using different hepatoma cell lines treated with ST. Lipid peroxidation and iron assays were performed using flow cytometry. Molecules involved in the ferroptosis pathway were detected by Western blotting. Finally, a lenvatinib-resistant cell line was established to evaluate the antiproliferative effects of ST.

RESULTS:

ST ethanol extract inhibited the growth of various hepatoma cell lines. A significant reduction in glutathione peroxidase 4 (GPX4) expression was observed following ST treatment, which was accompanied by increased lipid peroxidation and Fe2+ accumulation. ST induced ferroptosis mainly through heme oxygenase-1 (HO-1) expression. HO-1 knockdown reduced ST-induced lipid peroxidation and reversed GPX4 suppression. Acyl-CoA synthetase long-chain family member 4 (ACSL4) also participated in ST-induced ferroptosis. ST and lenvatinib combination showed an additive effect, and ST retained its potential anti-HCC efficacy in a lenvatinib-resistant cell line.

CONCLUSION:

This study demonstrated that the ethanol extract of ST inhibits hepatoma cell growth by inducing ferroptosis. ST displayed an additive effect with lenvatinib in Hep 3B cells and showed remarkable anti-HCC activity in lenvatinib-resistant Hep 3B cells. Collectively, the study shows that ST might have the potential to reduce lenvatinib use in clinical practice and salvage cases of lenvatinib resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinolinas / Extractos Vegetales / Carcinoma Hepatocelular / Solanum / Ferroptosis / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: J Ethnopharmacol Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Irlanda

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinolinas / Extractos Vegetales / Carcinoma Hepatocelular / Solanum / Ferroptosis / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: J Ethnopharmacol Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Irlanda