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Protein kinase A suppresses anti-proliferative effect of interferon-α in hepatocellular carcinoma by activation of protein tyrosine phosphatase SHP2.
J Biol Chem
January 2025
Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China. Electronic address:
Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer initiation and progression. Identifying signals that modulate the function of SHP2 can improve current therapeutic approaches for IFN-α/β in HCC. We showed that cAMP-dependent protein kinase A (PKA) suppresses IFN-α/β-induced JAK/STAT signaling by increasing the phosphatase activity of SHP2, promoting the dissociation of SHP2 from the receptor for activated C-kinase 1 (RACK1) and binding to STAT1.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of bisnoralcohol derivatives as novel IRF4 inhibitors for the treatment of multiple myeloma.
Eur J Med Chem
January 2025
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China. Electronic address:
Interferon regulatory factor 4 (IRF4) is specifically overexpressed in multiple myeloma (MM) and mediates MM progression and survival, making it an emerging target for MM treatment. However, no chemical entity with a defined structure capable of directly binding to and inhibiting IRF4 has been reported. We screened our small library of steroid analogs and identified bisnoralcohol (BA) derivative 18 as a novel hit compound capable of inhibiting IRF4, with an IC of 13.
View Article and Find Full Text PDFImmune regulation is more effective in the U937 inflammation model with mesenchymal stem cell extracellular vesicles stimulated by pro-inflammatory cytokines.
Cent Eur J Immunol
November 2024
Department of Stem Cell, Institute of Health Sciences, Kocaeli University, İzmit, Kocaeli, Turkey.
Mesenchymal stem cells (MSCs), which are multipotent adult cells with many therapeutic effects, can be derived from stromal tissues. MSCs also exert immunoregulatory effects through extracellular vesicles (EVs), cell membrane structures that carry paracrine factors. It is thought that the mediators (cytokines, growth factors, etc.
View Article and Find Full Text PDFMultilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment.
Pharmaceutics
October 2024
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile.
Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules' size, degradation, and pharmacokinetics.
View Article and Find Full Text PDFAllosteric inhibition of the tyrosine phosphatase SHP2 enhances the anti-tumor immunity of interferon α through induction of caspase-1-mediated pyroptosis in renal cancer.
Int Immunopharmacol
December 2024
Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China. Electronic address:
Interferon alpha (IFNα) leads to therapeutic effects on various tumors, especially renal cell cancer (RCC), by directly protecting against tumors cell proliferation or indirectly inducing an anti-tumor immune response. However, new combination therapies are needed to enhance the efficacy of IFNα and reduce its adverse effects during long-term treatment. In this study, we found that the anti-proliferative effects of IFNα on RCC cells in vitro and in vivo were greater after the allosteric inhibition of SHP2 by SHP099 than after treatment with enzymatic inhibitors of SHP2.
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