ArticleCell death & disease2011
Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Efficacy of traditional Chinese medicine on diabetic cardiomyopathy in animal models: a systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy.Life (Basel, Switzerland) · 2026Review
- Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.Cell death & disease · 2026Article
- CDK9 inhibitor A09-003 overcomes TRAIL resistance via dual Mcl-1 suppression in breast cancer cells.Discover oncology · 2026Article
- Effects of polyphenols on cancer cell progression mediated by inhibition of cyclin-dependent kinases (CDKs): the emerging drug targets in cancer.Archives of pharmacal research · 2025Review
- Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.Nature communications · 2025Article
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.Molecular cell · 2025Article
- Novel meriolin derivatives activate the mitochondrial apoptosis pathway in the presence of antiapoptotic Bcl-2.Cell death discovery · 2024Article
- Structure-guided design and cloning of peptide inhibitors targeting CDK9/cyclin T1 protein-protein interaction.Frontiers in pharmacology · 2024Article
- Phytochemicals as estrogen receptor modulators?-a commentary of a network pharmacology study of two commonly employed Chinese herbal medicines in non-small cell lung cancer treatment.Translational cancer research · 2023Article
- The novel CDK9 inhibitor, XPW1, alone and in combination with BRD4 inhibitor JQ1, for the treatment of clear cell renal cell carcinoma.British journal of cancer · 2023Article
- Therapeutic Strategies for Pancreatic-Cancer-Related Type 2 Diabetes Centered around Natural Products.International journal of molecular sciences · 2023Review
- Flavones and Related Compounds: Synthesis and Biological Activity.Molecules (Basel, Switzerland) · 2023Review
- CDK9 inhibitors downregulate DKK1 expression to suppress the metastatic potential of HCC cells.Genes & genomics · 2023Article
- Antitumor Effects of MicroencapsulatedMaterials (Basel, Switzerland) · 2023Article
- Discovery of a tetrahydroisoquinoline-based CDK9-cyclin T1 protein-protein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells.Genes & diseases · 2022Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Proteomic Signatures of Monocytes in Hereditary Recurrent Fevers.Frontiers in immunology · 2022Article
- Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics.Frontiers in genetics · 2022Review
- Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase.Cancers · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The wogonin-containing herb Scutellaria baicalensis has successfully been used for curing various diseases in traditional Chinese medicine. Wogonin has been shown to induce apoptosis in different cancer cells and to suppress growth of human cancer xenografts in vivo. However, its direct targets remain unknown. In this study, we demonstrate for the first time that wogonin and structurally related natural flavones, for example, apigenin, chrysin and luteolin, are inhibitors of cyclin-dependent kinase 9 (CDK9) and block phosphorylation of the carboxy-terminal domain of RNA polymerase II at Ser(2). This effect leads to reduced RNA synthesis and subsequently rapid downregulation of the short-lived anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) resulting in apoptosis induction in cancer cells. We show that genetic inhibition of Mcl-1 or CDK9 expression by siRNA is sufficient to mimic flavone-induced apoptosis. Pull-down and in silico docking studies demonstrate that wogonin directly binds to CDK9, presumably to the ATP-binding pocket. In contrast, wogonin does not inhibit CDK2, CDK4 and CDK6 at doses that inhibit CDK9 activity. Furthermore, we show that wogonin preferentially inhibits CDK9 in malignant compared with normal lymphocytes. Thus, our study reveals a new mechanism of anti-cancer action of natural flavones and supports CDK9 as a therapeutic target in oncology.
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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.