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Isoquinoline alkaloid berberine inhibits IL-5-dependent growth of pro-B Y16 cells through arresting cell cycle at G1 phase and inducing mitochondria-dependent apoptosis
Berberine, an isoquinoline alkaloid, has been reported to have several pharmacological properties including anti-inflammation and anti-cancer. Interleukin (IL)-5 is a Th2 cytokine involved in the eosinophilic inflammation. In this study, we investigated the effect of berberine on IL-5-dependent proliferation or survival of pro-B Y16 cells. Berberine inhibited IL-5-dependent proliferation of Y16 cells in the presence of serum with an IC50 value of 13µM. This effect of berberine was associated with an arrest of cell cycle at G1 phase, which was coincided with down-regulation of cyclins D3 and E2 as well as cyclin-dependent kinase (Cdk)-4, but also up-regulation of CDK inhibitory proteins of p21/Cip1 and p27/Kip1. Furthermore, the alkaloid inhibited IL-5-induced survival of Y16 cells without serum, showing an IC50 value of 18µM. In the TUNEL assay and Annexin V-FITC/PI double staining, morphological characteristics of apoptosis, including DNA fragmentation and plasma membrane disruption, were observed. Moreover, berberine dose-dependently decreased mitochondrial membrane potential, which was substantially correlated to down-regulation of anti-apoptotic bcl-2 family of Bcl-2 and Mcl-1. Taken together, berberine inhibited IL-5-dependent proliferation of Y16 cells through arresting cell cycle at G1 phase and also decreased IL-5-induced survival of the cells through mitochondria-dependent apoptosis.