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.