Purging effect of dibutyl phthalate on leukemia cells involves fas independent activation of caspase-3/CPP32 protease.
We previously found that dibutyl phthalate (DBP) had a pharmacological activity in eliminating tumor cells and could be used as a purging agent in autologous bone marrow transplantation. In this study, we show that DBP can induce apoptosis in MO7e and U937 leukemia cell lines. Treatment of these cells with DBP up-regulates cellular activity of caspase-3/CPP32 and causes apoptosis rapidly as determined by cell viability and dUTP nick end labeling assay. Activation of caspase-3/CPP32 and cleavage of poly(ADP-ribose) polymerase were determined in DBP-induced apoptosis of leukemia cells. However, DBP treatment did not induce the expression of fas. Two caspase inhibitors, z-VAD-fmk and N-acetyl-Asp-Glu-Val-Asp-aldehyde partly blocked the cell death of MO7e cells induced by DBP. These results suggest that fas-independent activation of caspase-3 protease plays important roles in the purging effect of DBP on leukemia cells.
Wang
Li-Sheng
LS
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. wangls@nic.bmi.ac.cn
Liu
Hong-Jun
HJ
Zhang
Jin-Hui
JH
Wu
Chu-Tse
CT
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D003993:Dibutyl Phthalate / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D020287:In Situ Nick-End Labeling; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D000596:Amino Acids; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; D003993:Dibutyl Phthalate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases