ArticleDiscover oncology2023
Artesunate alleviates 5-fluorouracil-induced intestinal damage by suppressing cellular senescence and enhances its antitumor activity.
Article in Discover oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Multifaceted Attack Networks of Artemisinin in Reversing Chemoresistance in Colorectal Cancer.Molecules (Basel, Switzerland) · 2026Review
- Plant Terpenoids in Combination with Conventional Therapeutics in Colorectal Cancer: A Promising Option.Current oncology reports · 2025Review
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- Exploring the Chemopreventive Potential ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Proteomic Analysis Identifies Multiple Mechanisms of 5-Fluorouracil-Induced Gut Mucositis in Mice.Cancers · 2024Article
- Review
- Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms.Antioxidants (Basel, Switzerland) · 2024Review
- Identification of Novel Protein Biomarkers and Drug Targets for Acne Vulgaris by Integrating Human Plasma Proteome with Genome-Wide Association Data.Journal of inflammation research · 2024Article
- Anti-tumor mechanism of artesunate.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundColorectal cancer (CRC) is one of the most prevalent diagnosed malignancies and one of the leading causes of cancer-related deaths worldwide. 5-Fluorouracil (5-FU) and its combination regimen are commonly used as primary chemotherapeutic agents for advanced CRC. Intestinal mucositis is one of the most frequent side effects of 5-FU. Artesunate (Arte) is derived from the wormwood plant Artemisia annua. Arte is not only effective against malaria but also diabetes, atherosclerosis, inflammation, and other conditions. The mechanism by which 5-FU damages the intestinal tract is unclear, and there is no standard treatment for diarrhea caused by 5-FU. Therefore, it is critical to discover novel and promising therapeutic drugs for 5-FU side effect treatment.
methodsThe morphology and expression of genes and proteins associated with the aging of HUVECs, HIECs, and intestinal tissues were compared to the those of the control group. The cell lines and tissues were evaluated by SA-β-Gal staining, Western blotting, and RT‒qPCR. HIEC and HCT116 cell viability was assessed in vitro by a CCK-8 assay and in vivo by a subcutaneous tumor mouse assay. Tumor cell proliferation and apoptosis was evaluated by immunohistochemistry.
resultsHere, we report that Arte alleviates the adverse side effects caused by 5-FU in intestinal tissue, and that 5-FU-induced intestinal damage is associated with drug-induced chemical inflammation and an increase in the proportion of senescent cells. Arte decreases the ratio of SA-β-Gal-positive cells and downregulated the expression of aging-related proteins (p53, p16) and aging-related genes (p53, p21). Mechanistically, Arte relieves intestinal injury by inhibiting mTOR expression, which is associated with the regulation of aging. Moreover, Arte suppresses the p38MAPK and NF-κB signaling pathways, which are related to inflammation regulation. In addition, the combined therapy of Arte plus 5-FU significantly decreases cancer cell viability in vitro. Arte and 5-FU synergistically reduce the growth of colorectal cancer (CRC) xenografts in vivo.
conclusionsOverall, our findings point to the crucial treatment effect of Arte on inflammation, intestinal cell senescence, and CRC cell proliferation and offer a new option for CRC treatment.
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