ArticleThe Journal of biological chemistry2012
Wogonin and related natural flavones overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein resistance of tumors by down-regulation of c-FLIP protein and up-regulation of TRAIL receptor 2 expression.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Escaping cell death via TRAIL decoy receptors: a systematic review of their roles and expressions in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- A Review on Hepatoprotective Effect of Chrysin: Preclinical Implications and Molecular Cascades Came into Focus.Current diabetes reviews · 2026Review
- Synergistic anticancer effects of Chrysin and trastuzumab in HER2-Positive breast cancer cells.Scientific reports · 2025Article
- Advances in nanocarrier-mediated delivery of chrysin: Enhancing solubility, bioavailability, and anticancer efficacy.BioImpacts : BI · 2025Review
- Flavonoids as Chemosensitizers in Leukemias.Advances in experimental medicine and biology · 2025Review
- Clinical research, mechanisms, and prospects of flavonoids from HerbaFrontiers in pharmacology · 2025Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- TRAIL-Sensitizing Effects of Flavonoids in Cancer.International journal of molecular sciences · 2023Review
- Therapeutic Strategies for Pancreatic-Cancer-Related Type 2 Diabetes Centered around Natural Products.International journal of molecular sciences · 2023Review
- Apigenin improves cytotoxicity of antiretroviral drugs against HTLV-1 infected cells through the modulation of AhR signaling.NeuroImmune pharmacology and therapeutics · 2023Article
- Santin (5,7-Dihydroxy-3,6,4'-Trimetoxy-Flavone) Enhances TRAIL-Mediated Apoptosis in Colon Cancer Cells.Life (Basel, Switzerland) · 2023Article
- Phytochemicals as Immunomodulatory Agents in Melanoma.International journal of molecular sciences · 2023Review
- Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment.World journal of gastroenterology · 2022Review
- Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin.Cancer cell international · 2021Review
- The Hallmarks of Flavonoids in Cancer.Molecules (Basel, Switzerland) · 2021Review
- Bone mesenchymal stem cells derived extracellular vesicles promote TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p.Cancer biomarkers : section A of Disease markers · 2021Article
- Targeting Protein Kinases Degradation by PROTACs.Frontiers in chemistry · 2021Review
- Inhibition of autophagy flux by sertraline attenuates TRAIL resistance in lung cancer via death receptor 5 upregulation.International journal of molecular medicine · 2020Article
- Dietary Polyphenols in Cancer Chemoprevention: Implications in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2020Review
- Flavonoids: New Frontier for Immuno-Regulation and Breast Cancer Control.Antioxidants (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that kills various tumor cells without damaging normal tissues. However, many cancers remain resistant to TRAIL. To overcome TRAIL resistance, combination therapies using sensitizers of the TRAIL pathway would be an efficacious approach. To investigate potential sensitizers of TRAIL-induced apoptosis, we used TRAIL-resistant human T cell leukemia virus type 1 (HTLV-1)-associated adult T cell leukemia/lymphoma (ATL) cells as a model system. So far, HTLV-1-associated ATL is incurable by presently known therapies. Here, we show that wogonin and the structurally related natural flavones apigenin and chrysin break TRAIL resistance in HTLV-1-associated ATL by transcriptional down-regulation of c-FLIP, a key inhibitor of death receptor signaling, and by up-regulation of TRAIL receptor 2 (TRAIL-R2). This effect is mediated through transcriptional inhibition of the p53 antagonist murine double minute 2 (Mdm2), leading to an increase in p53 levels and, consequently, to up-regulation of the p53 target gene TRAIL-R2. We also show that these flavones can sensitize to TNFα- and CD95-mediated cell death. Furthermore, we show that wogonin, apigenin, and chrysin also enhance TRAIL-mediated apoptosis in other human cancer cell lines including breast cancer cell line MDA-MB-231, colon cancer cell line HT-29, hepatocellular carcinoma cell line HepG2, melanoma cell line SK-MEL-37, and pancreatic carcinoma cell line Capan-1 by the same mechanism. Thus, our study suggests the potential use of these flavones as an adjuvant for TRAIL-mediated anticancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.