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Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3.
- Source :
- Phytomedicine; Jan2024, Vol. 123, pN.PAG-N.PAG, 1p
- Publication Year :
- 2024
-
Abstract
- • Pim-3 was highly expressed in ESCC and played an oncogenic role. • Pim-3 enhanced cell proliferation and tumor development by phosphorylating MAPK1 at T185 and Y187. • The deletion of Pim-3 induced apoptosis with upregulated cleaved caspase-9 and lower p-BAD<superscript>S112</superscript> levels. • Corynoline directly bound with Pim-3, inhibiting its activity, and surpressed ESCC growth. Esophageal squamous cell carcinoma (ESCC) is an aggressive and deadly malignancy characterized by late-stage diagnosis, therapy resistance, and a poor 5-year survival rate. Finding novel therapeutic targets and their inhibitors for ESCC prevention and therapy is urgently needed. We investigated the proviral integration site for maloney murine leukemia virus 3 (Pim-3) protein levels using immunohistochemistry. Using Methyl Thiazolyl Tetrazolium and clone formation assay, we verified the function of Pim-3 in cell proliferation. The binding and inhibition of Pim-3 by corynoline were verified by computer docking, pull-down assay, cellular thermal shift assay, and kinase assay. Cell proliferation, Western blot, and a patient-derived xenograft tumor model were performed to elucidate the mechanism of corynoline inhibiting ESCC growth. Pim-3 was highly expressed in ESCC and played an oncogenic role. The augmentation of Pim-3 enhanced cell proliferation and tumor development by phosphorylating mitogen-activated protein kinase 1 (MAPK1) at T185 and Y187. The deletion of Pim-3 induced apoptosis with upregulated cleaved caspase-9 and lower Bcl2 associated agonist of cell death (BAD) phosphorylation at S112. Additionally, binding assays demonstrated corynoline directly bound with Pim-3, inhibiting its activity, and suppressing ESCC growth. Our findings suggest that Pim-3 promotes ESCC progression. Corynoline inhibits ESCC progression through targeting Pim-3. [Display omitted] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09447113
- Volume :
- 123
- Database :
- Supplemental Index
- Journal :
- Phytomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 174794091
- Full Text :
- https://doi.org/10.1016/j.phymed.2023.155235