ArticleActa pharmacologica Sinica2021
Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 2 of them syntheses that pooled it.
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Who cites it
170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 294 citations in OpenAlex.
- The Role of Artemisinin and its Derivatives in Cancer Therapy via Ferroptosis: A Systematic Review ofAnti-cancer agents in medicinal chemistry · 2026Pooled it
- Mechanism and role of ferroptosis in the development of gastric cancer.Clinical and experimental medicine · 2025Pooled it
- Article
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Inhibition or induction of gastrointestinal tumors by ferroptosis and intervention by herbal extracts (Review).Oncology letters · 2026Review
- Artesunate in Ferroptosis and Cuproptosis Regulation: Context-Dependent Mechanisms, Interplay, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Repurposing approved drugs as ferroptosis modulators: a critical review of clinical trials in cancer and neurodegeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- BRSK2 accumulation mediated by TRIM28 accelerates hepatocellular carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway.Molecular and cellular biochemistry · 2026Article
- Targeting ferroptosis to overcome drug resistance in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The evaluation of biological effects of artesunate on ovarian cancer using three-dimensional cell culture methods.Cell and tissue banking · 2026Article
- Label-free proteomics and single-cell mass cytometry analysis of 5 immune tissues from mice with artesunate administration reveal immunosuppression of artesunate via BST2 and MDSCs.Fundamental research · 2026Article
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
- Exploring Synergistic Potential of Sorafenib and Atorvastatin to Launch Apoptosis and Ferroptosis-driven Mixed Cell Death Mechanism in Colorectal Cancer.AAPS PharmSciTech · 2026Article
- Artesunate directly targeting MMP9 to reduce angiogenesis and increase CD8 + T cell infiltration inhibits hepatocellular carcinoma.Cancer cell international · 2026Article
- Synthesis and Biological Evaluation of Isomeric Artemisinin Trimers as Novel Antitumor Agents.Molecules (Basel, Switzerland) · 2026Article
- Enocyanin Synergistically Enhances Sorafenib Sensitivity in Hepatocellular Carcinoma via Ferroptosis Induction Associated with p62/Keap1/Nrf2/HO-1 Pathway Inhibition.Current issues in molecular biology · 2026Article
- Dihydroartemisinin Induces Ferroptosis in Uveal Melanoma Cells Through the HO-1 and xCT/GPX4 Signaling Pathways.International journal of molecular sciences · 2026Article
- Liproxstatin-1 Attenuates Retinal Ischemia-Reperfusion Injury by Suppressing EGR1-Mediated Ferroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Anti-cancer mechanism of traditional Chinese medicine natural products targeting ferroptosis.Chinese medicine · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.
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