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China","award":["shslczdzk01201"],"award-info":[{"award-number":["shslczdzk01201"]}]},{"name":"National Natural Science Foundation of China","award":["zyyzdxk-2023060"],"award-info":[{"award-number":["zyyzdxk-2023060"]}]},{"name":"Shandong Province Key R&amp;D Program (Major Science and Technology Innovation Project","award":["82374188"],"award-info":[{"award-number":["82374188"]}]},{"name":"Shandong Province Key R&amp;D Program (Major Science and Technology Innovation Project","award":["2021CXGC010509"],"award-info":[{"award-number":["2021CXGC010509"]}]},{"name":"Shandong Province Key R&amp;D Program (Major Science and Technology Innovation Project","award":["20DZ2272200"],"award-info":[{"award-number":["20DZ2272200"]}]},{"name":"Shandong Province Key R&amp;D Program (Major Science and Technology Innovation Project","award":["shslczdzk01201"],"award-info":[{"award-number":["shslczdzk01201"]}]},{"name":"Shandong Province Key R&amp;D Program (Major Science and Technology Innovation 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Medicine","award":["zyyzdxk-2023060"],"award-info":[{"award-number":["zyyzdxk-2023060"]}]},{"name":"State Administration of Traditional Chinese Medicine of The Peoples Republic of China","award":["82374188"],"award-info":[{"award-number":["82374188"]}]},{"name":"State Administration of Traditional Chinese Medicine of The Peoples Republic of China","award":["2021CXGC010509"],"award-info":[{"award-number":["2021CXGC010509"]}]},{"name":"State Administration of Traditional Chinese Medicine of The Peoples Republic of China","award":["20DZ2272200"],"award-info":[{"award-number":["20DZ2272200"]}]},{"name":"State Administration of Traditional Chinese Medicine of The Peoples Republic of China","award":["shslczdzk01201"],"award-info":[{"award-number":["shslczdzk01201"]}]},{"name":"State Administration of Traditional Chinese Medicine of The Peoples Republic of China","award":["zyyzdxk-2023060"],"award-info":[{"award-number":["zyyzdxk-2023060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hepatocellular carcinoma (HCC), currently ranking as the third most lethal malignancy, poses a grave threat to human health. Ferroptosis, a form of programmed cell demise, has emerged as a promising therapeutic target in HCC treatment. In this study, we investigated the impact of ginsenoside RK1 on ferroptosis induction in HCC cells and elucidated the underlying mechanisms. Methods: The HCC cell line HepG2 was utilized to evaluate the effects of ginsenoside RK1. Distinct dosages of ginsenoside RK1 (25 \u03bcM, 50 \u03bcM, and 100 \u03bcM) were selected based on half-maximal inhibitory concentration (IC50) values. Cellular viability was assessed using a CCK8 assay, cytotoxicity was measured via lactate dehydrogenase (LDH) release assay, and colony-forming ability was evaluated using the clone formation assay. Various inhibitors targeting apoptosis (Z-VAD-FMK 20 \u03bcM), necrosis (Nec-1, 10 \u03bcM), and ferroptosis (Fer-1, 10 \u03bcM; Lip-1, 1 \u03bcM) were employed to assess ginsenoside RK1\u2019s impact on cell demise. Intracellular levels of key ions, including glutathione (GSH), malondialdehyde (MDA), and iron ions, were quantified, and the protein expression levels of ferroptosis-related genes were evaluated. The sensitivity of HCC cells to ferroptosis induction by ginsenoside RK1 was examined following the overexpression and silencing of the aforementioned target genes. Results: Ginsenoside RK1 exhibited an inhibitory effect on HCC cells with an IC50 value of approximately 20 \u03bcM. It attenuated cellular viability and colony-forming capacity in a dose-dependent manner, concurrently reducing intracellular GSH levels and increasing intracellular Malondialdehyde (MDA) and iron ion contents. Importantly, cell demise induced by ginsenoside RK1 was specifically counteracted by ferroptosis inhibitors. Furthermore, the modulation of Ferroptosis suppressor protein 1 (FSP1) expression influenced the ability of ginsenoside RK1 to induce ferroptosis. FSP1 overexpression or silencing enhanced or inhibited ferroptosis induction by ginsenoside RK1, respectively. Conclusions: Ginsenoside RK1 enhances ferroptosis in hepatocellular carcinoma through an FSP1-dependent pathway.<\/jats:p>","DOI":"10.3390\/ph17070871","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:04:18Z","timestamp":1719986658000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Ginsenoside RK1 Induces Ferroptosis in Hepatocellular Carcinoma Cells through an FSP1-Dependent Pathway"],"prefix":"10.3390","volume":"17","author":[{"given":"Yulang","family":"Jiang","sequence":"first","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Internal Medicine in Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9915-3566","authenticated-orcid":false,"given":"Yongxin","family":"Yu","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Internal Medicine in Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Pan","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Internal Medicine in Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Internal Medicine in Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-7283","authenticated-orcid":false,"given":"Mingyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Internal Medicine in Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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