Induction of apoptosis, p53 and heme oxygenase-1 by cytotoxic prostaglandin delta12-PGJ2 in transformed endothelial cells.
Delta12-prostaglandin (PG)J2, which has been reported to have potent growth inhibitory activity in various tumor cells, induced apoptosis at 5 microg/ml culture medium in transformed mouse endothelial (F2) cells. Immunoblot analysis using anti-p53 or anti-WAF1 antibodies demonstrated that these two proteins had increased following delta12-PGJ2 treatment in F2 cells. Western blotting analysis using anti-heme oxygenase-1 (heat shock protein (HSP)32) antibody also revealed that delta12-PGJ2 induced HSP32 formation in F2 cells. HSP32 was also induced by heat shock treatment at 43 degrees C for 90 min. In contrast, HSP72 was not induced by heat shock or by delta12-PGJ2 treatment. In agreement with these findings, HSP32 immunofluorescence in the cytoplasm of F2 cells was intensified by delta12-PGJ2 treatment. More intense HSP32 immunoreactivity was similarly observed after heat shock treatment. These results suggest that delta12-PGJ2 caused the apoptotic cell death of F2 cells, which involved a certain process required for p53 or HSP32 induction.
Ikai
K
K
Department of Dermatology, Kyoto University Graduate School of Medicine, Japan. yuta@kuhp.kyoto-u.ac.jp
Kudo
H
H
Toda
K
K
Fukushima
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002461:Cell Line, Transformed / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1; D010105:Oxygenases; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53; C037112:9-deoxy-delta-9-prostaglandin D2; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C491523:Hmox1 protein, rat; D015230:Prostaglandin D2