ArticleOxidative medicine and cellular longevity2022
Theaflavin-3,3'-Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts.
Article in Oxidative medicine and cellular longevity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 31 citations in OpenAlex.
- Natural products mediate ferroptosis and immune microenvironment-linked sensitization in osteosarcoma: from chemotherapy resistance to combined therapeutic transformation.Molecular diversity · 2026Review
- Research Progress on Chinese Herbal Medicine Components Targeting Ferroptosis for Cancer Therapy.Molecules (Basel, Switzerland) · 2026Review
- Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review).Molecular medicine reports · 2026Review
- Theaflavin-3,3'-Digallate Targets Pin1 to Suppress Hepatocellular Carcinoma Malignant Proliferation Through Modulation of MAPK and PI3K/AKT Signaling Pathways In Vitro.Biomolecules · 2026Article
- Targeting Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review.Journal of cellular and molecular medicine · 2026Review
- Lenvatinib induces ferroptosis-related changes in osteosarcoma cells involving the p-STAT3/p53/xCT axis.Frontiers in oncology · 2026Article
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- Targeting Ferroptosis to Overcome Drug Resistance in Cancer: Molecular Mechanisms and Therapeutic Prospects.Biomolecules & therapeutics · 2026Review
- Screening of Theaflavins That Inhibit Proliferation of Nasopharyngeal Carcinoma Cells Through Metabolomics Approaches.Food science & nutrition · 2025Article
- A Comprehensive Review of Theaflavins: Physiological Activities, Synthesis Techniques, and Future Challenges.Food science & nutrition · 2025Review
- Theaflavin inhibits the malignant phenotype of human anaplastic thyroid cancer 8305C cells by regulating lipid metabolism via PI3K/AKT signaling.Translational cancer research · 2025Article
- Theaflavin-3,3'-digallate protects against myocardial ischemia/reperfusion injury and hypoxia/reoxygenation injury by activating the PI3K/Akt/mTOR pathway.Journal of molecular histology · 2025Article
- Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway.Journal of bone oncology · 2025Article
- Modulating Ferroptosis in Aging: The Therapeutic Potential of Natural Products.Journal of aging research · 2025Review
- Non-coding RNA: A key regulator in the Glutathione-GPX4 pathway of ferroptosis.Non-coding RNA research · 2024Review
- Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects.Experimental hematology & oncology · 2024Review
- Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis-A Systematic Review.Antioxidants (Basel, Switzerland) · 2024Review
- Oridonin-induced ferroptosis and apoptosis: a dual approach to suppress the growth of osteosarcoma cells.BMC cancer · 2024Article
- Article
- Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma.Asian journal of pharmaceutical sciences · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
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Abstract
Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3'-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.
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