Prunetin Protects Against Dexamethasone-Induced Pancreatic Β-Cell Apoptosis via Modulation of p53 Signaling Pathway

dc.contributor.authorSuwattanee Kooptiwuten_US
dc.contributor.authorKanokwan Samonen_US
dc.contributor.authorNamoiy Sempraserten_US
dc.contributor.authorKanchana Suksrien_US
dc.contributor.authorPa Thai Yenchitsomanusen_US
dc.contributor.otherFaculty of Medicine, Siriraj Hospital, Mahidol Universityen_US
dc.description.abstract© The Author(s) 2020. Long-term administration of dexamethasone results in insulin resistance and pancreatic β-cell apoptosis. Prunetin (an O-methylated isoflavone, a type of flavonoid) is demonstrated to protect diabetes, but the molecular mechanism of this protection is still unclear. This study thus aims to investigate how prunetin protects against dexamethasone-induced pancreatic β-cell apoptosis. Rat insulinoma (INS-1) cells were cultured in medium with or without dexamethasone in the presence or absence of prunetin or pifithrin-α, a p53 inhibitor. Cell apoptosis was measured by Annexin V/propidium iodide staining. Dexamethasone significantly induced INS-1 apoptosis but dexamethasone plus prunetin significantly reduced INS-1 apoptosis. Dexamethasone-treated INS-1 upregulated p53 protein expression; the induction of p53 was also reduced in the presence of RU486, a glucocorticoid receptor (GR) inhibitor. This suggested that dexamethasone induced P53 via GR. Dexamethasone-treated INS-1 significantly increased p53, Bax, and Rb protein expressions, whereas treatments of dexamethasone plus prunetin or pifithrin-α significantly decreased these protein expressions. In addition, dexamethasone significantly decreased B-cell lymphoma 2 (Bcl2), while dexamethasone plus prunetin or pifithrin-α significantly increased Bcl2. Dexamethasone significantly increased caspase-3 activity while co-treatment of dexamethasone plus prunetin or pifithrin-α significantly decreased caspase-3 activity to the control level. Taken together, our results revealed that prunetin protected against dexamethasone-induced pancreatic β-cells apoptosis via modulation of the p53 signaling pathway.en_US
dc.identifier.citationNatural Product Communications. Vol.15, No.4 (2020)en_US
dc.rightsMahidol Universityen_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titlePrunetin Protects Against Dexamethasone-Induced Pancreatic Β-Cell Apoptosis via Modulation of p53 Signaling Pathwayen_US