Homoharringtonine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of telomerase.
Homoharringtonine (HHT), first isolated from the Chinese evergreen Cephalotaxus Harringtonia, has been shown inhibiting activity in leukemia in initial studies in China and in later studies in the US, but the detailed mechanism of action is still unclear. The goal of the experiments shown here is to explore the effect of HHT on the telomerase activity and apoptosis of human leukemia HL-60 cells. The telomerase activity of HL-60 cells was examined by the telomeric repeat amplification protocol (TRAP)--an enzyme-linked immunosorbent assay (ELISA). Apoptosis was analyzed by morphological observation, DNA agarose gel electrophoresis, flow cytometry (FCM), and TdT-mediated dUTP-biotin nick end labeling (TUNEL). After treatment with HHT at 5-500 microg/l for 48 hours, the level of telomerase activity in HL-60 cells decreased in a dose-and time-dependent manner. Simultaneously, HL-60 cells underwent apoptosis. In conclusion, our data suggest that HHT can inhibit the telomerase content of HL-60 cells effectively and induce apoptosis.
Xie
Wan-Zhuo
WZ
First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China. xiewanz@yahoo.com.cn
Lin
Mao-Fang
MF
Huang
He
H
Cai
Zhen
Z
D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018922:HL-60 Cells; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D019098:Telomerase / Q000378:metabolism*
D006248:Harringtonines; D000077863:Homoharringtonine; D019098:Telomerase