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Κυριακή 14 Ιουλίου 2019

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as Berberis. Berberine is usually found in the roots, rhizomes, stems, and bark. Due to berberine's strong yellow color, Berberis species were used to dye wool, leather, and wood



Berberine enhances posttranslational protein stability of p21/cip1 in breast cancer cells via down-regulation of Akt

Abstract

Berberine has shown anticancer properties and has potential for a chemopreventive and/or chemotherapeutic agent for breast cancer. Berberine showed cytotoxicity to breast cancer cells, with an increase in the levels of p21/cip1 and p27/kip1, cyclin-dependent kinase inhibitors (CDKI), but mechanisms involved in up-regulating these molecules are largely unknown. Herein, we studied the key regulatory mechanisms involved in berberine-mediated up-regulation of p21/cip1 and p27/kip1. Berberine treatment for 24 and 48 h decreased the number of cells by 44–84% (P < 0.0001) and 38–78% (P < 0.0001), and increased cell death by 12–17% (P < 0.005) and 38–78% (P < 0.0001) in MCF-7 and MDA-MB-231 cells, respectively. Cells were arrested in G1 phase by berberine which was accompanied with up-regulation of mRNA and protein level of both p21/cip1 and p27/kip1. Berberine decreased the expression of protein levels of cyclin D1, cyclin E, CDK2, CDK4, and CDK6 to cause G1 phase arrest. Berberine caused nuclear localization of p21/cip1 in both the cell lines. Our data for the first time showed that the post-translational stability of both the proteins was strongly increased by berberine as examined by cycloheximide chase assay. Inhibition of Akt was associated with berberine-mediated up-regulation of p21/cip1 and also led to a decrease in cell viability accompanied with significant G1 phase cell cycle arrest. Our study revealed that berberine not only up-regulates mRNA and protein levels of p21/cip1 and p27/kip1 but also increases their nuclear localization and post-translational protein stability. Further, Akt inhibition was found to mediate berberine-mediated up-regulation of p21/cip1 but not the p27/kip1.


Berberine

Description

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as Berberis. Berberine is usually found in the roots, rhizomes, stems, and bark. Due to berberine's strong yellow color, Berberis species were used to dye wool, leather, and wood. Wikipedia
FormulaC20H18NO4+
Molar mass336.3612 g/mol
Boiling point145 °C
AppearanceYellow solid
PubChem CID2353

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