ArticleCell death & disease2018
Discovery of a small-molecule protein kinase Cδ-selective activator with promising application in colon cancer therapy.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 123 citations in OpenAlex.
- Jurkat T-Cell Antigen-Independent Elimination of PMA-Activated Neuroblastoma Cells Is Triggered by CCL2/CCR2, Depends Upon Lipid Raft LFA1/ICAM1 Immune Synapses, Is Mediated by m-TRAIL and Is Augmented by the TrkAIII Oncoprotein.International journal of molecular sciences · 2026Article
- Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma.iScience · 2026Article
- PMA exerts anti-leukemia effect in PhCancer cell international · 2025Article
- Extraction optimization and reactivity of 7α-acetoxy-6β-hydroxyroyleanone and ability of its derivatives to modulate PKC isoforms.Scientific reports · 2024Article
- Article
- A human proteogenomic-cellular framework identifies KIF5A as a modulator of astrocyte process integrity with relevance to ALS.Communications biology · 2023Article
- Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator.International journal of molecular sciences · 2023Article
- PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation.Heliyon · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- BBIT20 inhibits homologous DNA repair with disruption of the BRCA1-BARD1 interaction in breast and ovarian cancer.British journal of pharmacology · 2021Article
- TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models.The EMBO journal · 2020Article
- Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones.International journal of molecular sciences · 2020Article
- SLMP53-1 Inhibits Tumor Cell Growth through Regulation of Glucose Metabolism and Angiogenesis in a P53-Dependent Manner.International journal of molecular sciences · 2020Article
- The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis.Mediators of inflammation · 2020Review
- Royleanone Derivatives FromFrontiers in pharmacology · 2020Article
- Tumor suppressive role for kinases phosphorylating p53 in DNA damage-induced apoptosis.Cancer science · 2018Review
- Improving anticancer activity towards colon cancer cells with a new p53-activating agent.British journal of pharmacology · 2018Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation. In HCT116 colon cancer cells, Roy-Bz specifically triggered the translocation of PKCδ but not other phorbol ester responsive PKCs. Roy-Bz caused a marked inhibition in migration of HCT116 cells in a PKCδ-dependent manner. Additionally, the impairment of colonosphere growth and formation, associated with depletion of stemness markers, indicate that Roy-Bz also targets drug-resistant cancer stem cells, preventing tumor dissemination and recurrence. Notably, in xenograft mouse models, Roy-Bz showed a PKCδ-dependent antitumor effect, through anti-proliferative, pro-apoptotic, and anti-angiogenic activities. Besides, Roy-Bz was non-genotoxic, and in vivo it had no apparent toxic side effects. Collectively, our findings reveal a novel promising anticancer drug candidate. Most importantly, Roy-Bz opens the way to a new era on PKC biology and pharmacology, contributing to the potential redefinition of the structural requirements of isozyme-selective agents, and to the re-establishment of PKC isozymes as feasible therapeutic targets in human diseases.
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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.