Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-gamma ligands induces apoptosis on human myeloid leukemia cells in vitro.
The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-gamma ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.
Liu
J J
JJ
Department of Hematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R China.
Huang
R W
RW
Lin
D J
DJ
Peng
J
J
Wu
X Y
XY
Lin
Q
Q
Pan
X L
XL
Song
Y Q
YQ
Zhang
M H
MH
Hou
M
M
Chen
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002839:Chromans / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000096:biosynthesis*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D008024:Ligands; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D047495:PPAR gamma / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000970:Antineoplastic Agents; C494826:BAX protein, human; C107489:BIRC5 protein, human; D002839:Chromans; D015853:Cysteine Proteinase Inhibitors; D007155:Immunologic Factors; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; D000077288:Troglitazone; D015230:Prostaglandin D2