Platycodin D induces apoptosis and decreases telomerase activity in human leukemia cells.
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 microM, 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.
Kim
Mun-Ock
MO
Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Moon
Dong-Oh
DO
Choi
Yung Hyun
YH
Shin
Dong Yeok
DY
Kang
Ho Sung
HS
Choi
Byung Tae
BT
Lee
Jae-Dong
JD
Li
Wei
W
Kim
Gi-Young
GY
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*
D016271:Proto-Oncogene Proteins c-myc; D012503:Saponins; D014315:Triterpenes; C108953:platycodin D; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase