The peroxisome proliferator-activated receptor gamma ligand 15-deoxy-Delta12,14-prostaglandin J2 induces vascular endothelial growth factor in the hormone-independent prostate cancer cell line PC 3 and the urinary bladder carcinoma cell line 5637.
Cyclopentenone-prostaglandin derivatives, including the peroxisome-proliferator activated receptor gamma (PPARgamma) ligand 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), inhibit tumor cell growth in vitro and in vivo. As 15d-PGJ2 was found to stimulate the expression of vascular endothelial growth factor (VEGF) in endothelial cells, we investigated whether 15d-PGJ2 induces this angiogenic factor in the human androgen-independent PC 3 prostate and the 5637 urinary bladder carcinoma cell line. In PC 3 cells, 15d-PGJ2 caused a dose-dependent increase in VEGF mRNA expression, as determined by RT-PCR. Stimulation started after 6 h, and after 72 h, VEGF mRNA expression reached a maximum of 3.3+/-0.3 U, 4.4+/-0.3 U and 6.1+/-0.1 U with 1, 5 and 10 microM 15d-PGJ2, respectively. Between 12-72 h, VEGF protein production was stimulated by up to 2-fold with 5 and 10 microM 15d-PGJ2 as assessed by ELISA in PC 3 cell-conditioned medium. In 5637 cells, 15d-PGJ2 did not alter VEGF mRNA expression for up to 72 h. Thereafter, VEGF mRNA expression was transiently increased from 2.3+/-0.8 U in control cells to 4.6+/-0.5 U in 1 microM and 5.9+/-0.6 U in 5 microM 15d-PGJ2-treated cells. VEGF protein production was only moderately stimulated (1.7-fold). 10 microM 15d-PGJ2 had no effect on VEGF mRNA expression in 5637 cells, but effectively reduced viability in both cell lines. 15d-PGJ2 also increased PPARgamma mRNA expression in both cell lines. While in PC 3 cells, stimulation of PPARgamma mRNA expression occurred after 72 h, in 5637 cells, a transient stimulation took place after 6 h (4-fold). We demonstrated that 15d-PGJ2 induces VEGF in PC 3 and 5637 cancer cells. This might be important if PG-analogues are considered as antitumor agents.
Haslmayer
Petra
P
Department of Pathophysiology, University of Vienna, AKH, Vienna, Austria.
Thalhammer
Theresia
T
Jäger
Walter
W
Aust
Sylvia
S
Steiner
Georg
G
Ensinger
Christian
C
Obrist
Peter
P
D002470:Cell Survival; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008024:Ligands; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016228:Endothelial Growth Factors; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008222:Lymphokines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015230:Prostaglandin D2