ArticlePloS one2007
Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 109 citations in OpenAlex.
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- Artesunate regulates malignant progression of breast cancer cells via lncRNA TUG1/miR-145-5p/HOXA5 axis.PloS one · 2025Article
- Bibliometric and Visualized Analysis of Artemisinin and Its Derivatives in Cancer.Drug design, development and therapy · 2025Article
- Multiscale screening and identifying specific targets for artesunate in suppressing bladder cancer.Frontiers in pharmacology · 2025Article
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- Phytometabolites as modulators of breast cancer: a comprehensive review of mechanistic insights.Medical oncology (Northwood, London, England) · 2024Review
- Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.Frontiers in pharmacology · 2024Review
- Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity.International journal of molecular sciences · 2023Article
- Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells.Cell communication and signaling : CCS · 2023Article
- Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma.BMC cancer · 2022Article
- Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption.Nucleic acids research · 2021Article
- Artemisinin Inhibits the Migration and Invasion in Uveal Melanoma via Inhibition of the PI3K/AKT/mTOR Signaling Pathway.Oxidative medicine and cellular longevity · 2021Article
- Artemisinin-type drugs for the treatment of hematological malignancies.Cancer chemotherapy and pharmacology · 2021Review
- Artemisinin-type drugs for the treatment of hematological malignancies.Cancer chemotherapy and pharmacology · 2021Review
- Article
- Synthesis and Evaluation of Artemisinin-Based Hybrid and Dimer Derivatives as Antimelanoma Agents.ACS omega · 2020Article
- Retrospective study of small pet tumors treated with Artemisia annua and iron.International journal of oncology · 2020Article
- Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-malarial artesunate also exerts profound anti-cancer activity. The susceptibility of tumor cells to artesunate can be enhanced by ferrous iron. The transferrin receptor (TfR) is involved in iron uptake by internalization of transferrin and is over-expressed in rapidly growing tumors. The ATP-binding cassette (ABC) transporters ABCB6 and ABCB7 are also involved in iron homeostasis. To investigate whether these proteins play a role for sensitivity towards artesunate, Oncotest's 36 cell line panel was treated with artesunate or artesunate plus iron(II) glycine sulfate (Ferrosanol). The majority of cell lines showed increased inhibition rates, for the combination of artesunate plus iron(II) glycine sulfate compared to artesunate alone. However, in 11 out of the 36 cell lines the combination treatment was not superior. Cell lines with high TfR expression significantly correlated with high degrees of modulation indicating that high TfR expressing tumor cells would be more efficiently inhibited by this combination treatment than low TfR expressing ones. Furthermore, we found a significant relationship between cellular response to artesunate and TfR expression in 55 cell lines of the National Cancer Institute (NCI), USA. A significant correlation was also found for ABCB6, but not for ABCB7 in the NCI panel. Artesunate treatment of human CCRF-CEM leukemia and MCF7 breast cancer cells induced ABCB6 expression but repressed ABCB7 expression. Finally, artesunate inhibited proliferation and differentiation of mouse erythroleukemia (MEL) cells. Down-regulation of ABCB6 by antisense oligonucleotides inhibited differentiation of MEL cells indicating that artesunate and ABCB6 may cooperate. In conclusion, our results indicate that ferrous iron improves the activity of artesunate in some but not all tumor cell lines. Several factors involved in iron homeostasis such as TfR and ABCB6 may contribute to this effect.
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