Platycodin D induces apoptosis and decreases telomerase activity in human leukemia cells

Abstract

Platycodin D (PD) is a major constituent of triterpene saponins found in the root of Platycodon grandiflorum. Recent studies have demonstrated that PD is a potentially interesting candidate for use in cancer chemotherapy. However, the molecular mechanisms responsible for PD-induced telomerase inhibition remain to be poorly known. In this study, we examined the effects of PD treatment on telomerase activity in different human leukemia cell lines. At concentrations between 10 and 20 μM, PD exerted a dose-dependent direct cytotoxic effect and inhibition of telomerase activity via downregulation of hTERT expression. Because c-Myc and Sp1 are known to directly regulate transcription of hTERT, we also evaluated the expression and DNA binding activity of these proteins. PD treatment reduced c-Myc and Sp1 protein levels and DNA binding activities in a dose-dependent manner. We also observed that PD treatment downregulates the activation of Akt, thereby reducing the phosphorylation and nuclear translocation of hTERT. We conclude that PD has direct cytotoxic effect on human leukemia cells and suppresses telomerase activity through transcriptional and posttranslational suppression of hTERT.