Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel.
BACKGROUND
Paclitaxel, an antineoplastic drug, inhibits cell growth and cell cycle progression and induces apoptosis in human leukemia HL-60 cells. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis.


METHODS
We examined the cell morphology and apoptosis in HL-60 cells after exposure to paclitaxel and measured caspase-3 activities with or without z-VAD-fmk (a broad-spectrum caspase inhibitor) pretreatment by flow cytometric analysis and Western blotting.


RESULTS
Together, our results were (1) paclitaxel mainly induced G2/M cell cycle arrest in HL-60 cells (p<0.001); (2) time (p<0.001)- and dose-dependent (p<0.001) apoptosis of HL-60 cells was induced by paclitaxel; (3) in HL-60 cells, z-VAD-fmk blocked paclitaxel-induced apoptosis (12 h: p<0.001; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.001) and caspase-3 activation (12 h: p<0.05; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.01).


CONCLUSIONS
These results suggest that paclitaxel can induce G2/M cell cycle transition and apoptosis via caspase-3 activity in HL-60 cells.
Lu
Ko-Hsiu
KH
Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan, Republic of China.
Lue
Ko-Huang
KH
Liao
Hsien-Hua
HH
Lin
Keh-Liang
KL
Chung
Jing-Gung
JG
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D011480:Protease Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D017239:Paclitaxel