Effect of harringtonine on apoptotic cell death and cell cycle progression in human leukemia HL60 cells.
The mechanism of cell killing induced by harringtonine (HT) was investigated in HL60 cells by metabolic labeling studies, light and transmission electron microscopy, agarose gel electrophoresis of DNA and flow cytometry. At concentrations higher than 0.02 microM HT showed significant inhibition on cell growth and protein and DNA synthesis. Following exposure to HT, typical apoptotic cell death was observed from 1.5 to 4 h and it increased in both dose-and time-dependent fashion. This process was prevented by an intracellular calcium ion chelator. In addition, at 0.04 microM of HT the nonapoptotic cells delayed the progression of cell cycle through S and G2 phase and finally arrested in G1 phase. These results are important to understand the mechanism of action of HT and to improve the effect of HT in cancer chemotherapy.
First Department of Internal Medicine, Fukui Medical School, Japan.
Y P
YP
Liu
T
T
Ueda
A
A
Yoshida
H
H
Iwasaki
T
T
Nakamura
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D006248:Harringtonines / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006248:Harringtonines; D009363:Neoplasm Proteins; C062500:harringtonin; D007930:Leucine; D013936:Thymidine