ArticlePloS one2015
Gypenosides Synergistically Enhances the Anti-Tumor Effect of 5-Fluorouracil on Colorectal Cancer In Vitro and In Vivo: A Role for Oxidative Stress-Mediated DNA Damage and p53 Activation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 60 citations in OpenAlex.
- Tumor microenvironment responsive copper-doped carbon dots for synergistic chemotherapy and cuproptosis in laryngeal cancer.iScience · 2026Article
- The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches.Cancers · 2025Review
- Astemizole Exacerbates 5-Fluorouracil-Triggered Cardiotoxicity by Enhancing Ptgs2.Cardiovascular toxicology · 2025Article
- Chemical Profiling, Antioxidant, and Antiproliferative Activities of AlgerianCurrent topics in medicinal chemistry · 2025Article
- Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance.Chinese medicine · 2024Review
- Bacoside a inhibits the growth of glioma by promoting apoptosis and autophagy in U251 and U87 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- α‑Phellandrene enhances the apoptosis of HT‑29 cells induced by 5‑fluorouracil by modulating the mitochondria‑dependent pathway.Oncology reports · 2024Article
- Gypenoside induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and enhances T-cell antitumor immunity by inhibiting PD-L1 in gastric cancer.Frontiers in pharmacology · 2024Article
- Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance.Biomolecules & therapeutics · 2022Review
- LINC00092 Modulates Oxidative Stress and Glycolysis of Breast Cancer Cells via Pyruvate Carboxylase-Mediated AKT/mTOR Pathway.Oxidative medicine and cellular longevity · 2022Article
- Synergistic effects ofJournal of Cancer · 2022Article
- Gypenoside-Induced Apoptosis via the PI3K/AKT/mTOR Signaling Pathway in Bladder Cancer.BioMed research international · 2022Article
- Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression.Bioengineered · 2021Article
- Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis.Biomolecules · 2021Article
- Gypenosides improves nonalcoholic fatty liver disease induced by high-fat diet induced through regulating LPS/TLR4 signaling pathway.Cell cycle (Georgetown, Tex.) · 2020Article
- Article
- Veterinarians' attitudes towards use of nutraceuticals.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2019Article
- Natural gypenosides: targeting cancer through different molecular pathways.Cancer management and research · 2019Article
- Article
- Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1'-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators.Journal of the American Chemical Society · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objective5-Fluorouracil (5-Fu) has been widely used as a first-line drug for colorectal cancer (CRC) treatment but limited by drug resistance and severe toxicity. The chemo-sensitizers that augment its efficiency and overcome its limitation are urgently needed. Gypenosides (Gyp), the main components from Gynostemma pentaphyllum (Thunb.) Makino, has shown potential anti-tumor property with little side-effect. Here, we carefully explored the chemo-sensitization of Gyp to potentiate the anti-tumor effect of 5-Fu in vitro and in vivo. METHODOLOGY / PRINCIPAL
findings3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide tetrazolium assay and colony formation test reveal that Gyp could significantly enhance the 5-Fu-caused SW-480,SW-620 and Caco2 cells viability loss. Calcusyn analysis shows that Gyp acts synergistically with 5-Fu. Annexin V-PE/7-AAD staining indicates 5-Fu + Gyp could induce SW-480 cell apoptosis. The activations of caspase 3, caspase 9 and poly (ADP-ribose) polymerase (PARP) were involved in the process. Gyp was also found to up-regulate 5-Fu-caused phospho-p53 expression and thus augment 5-Fu-induced G0/G1 phase arrest. Gyp elevated intracellular ROS level, significantly enhanced 5-Fu-triggered DNA damage response as evidenced by flow cytometry, comet assay and the expression of Ser139-Histone H2A.X. Inhibition of ROS and p53 respectively reversed the cell death induced by 5-Fu + Gyp, suggesting the key roles of ROS and p53 in the process. Moreover, 5-Fu and Gyp in combination exhibits much superior tumor volume and weight inhibition on CT-26 xenograft mouse model in comparison to 5-Fu or Gyp alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation. Preliminary toxicological results show that 5-Fu + Gyp treatment is relatively safe.
conclusionsAs a potential chemo-sensitizer, Gyp displays a splendid synergistic effect with 5-Fu to inhibit cancer cell proliferation and tumor growth. By using 5-Fu and Gyp in combination would be a promising therapeutic strategy for CRC treatment.
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