Induction of p53 and apoptosis by delta 12-PGJ2 in human hepatocarcinoma SK-HEP-1 cells. 1995

J H Lee, and H S Kim, and S Y Jeong, and I K Kim
Department of Biochemistry, Catholic University Medical College, Seoul, South Korea.

Human hepatocarcinoma cells (SK-HEP-1) were induced to die through apoptosis by treatment with delta 12-prostaglandin (PG)J2, as characterized by the appearance of a typical DNA ladder. The induction of apoptosis by delta 12-PGJ2 was specifically blocked by cycloheximide (CHX). Western analysis using anti-p53 or anti-WAF1 monoclonal antibodies demonstrated that these two protein levels were increased 3 h after delta 12-PGJ2 treatment, and accumulated for up to 12 h. The induction of p53 protein seemed to be dependent on the increase of p53 mRNA level, which was inhibited by CHX treatment. However, delayed addition of CHX after delta 12-PGJ2 treatment failed to affect both p53 mRNA levels and DNA fragmentation following delta 12-PGJ2 treatment, indicating that the inhibition of p53 synthesis may contribute to the protective effect of CHX against delta 12-PGJ2-mediated cytotoxicity. Therefore, our results suggest that the initial events caused by delta 12-PGJ2, leading ultimately to SK-HEP-1 cell death, involve a certain process required for p53 induction. However, the finding that delta 12-PGJ2 is also active against Hep 3B cells which are devoid of a functional p53 indicates that p53 may not be the critical requirement for inducing apoptosis by delta 12-PGJ2.

UI MeSH Term Description Entries
D011465 Prostaglandins, Synthetic Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity. PG Analog,PG Analogs,Prostaglandin Analog,Prostaglandin Analogs,Prostaglandin Analogue,Synthetic Prostaglandin,Prostaglandin Analogues,Synthetic Prostaglandins,Analog, PG,Analog, Prostaglandin,Analogs, PG,Analogs, Prostaglandin,Analogue, Prostaglandin,Analogues, Prostaglandin,Prostaglandin, Synthetic
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003513 Cycloheximide Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. Actidione,Cicloheximide
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015230 Prostaglandin D2 The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects. 11-Dehydroprostaglandin F2alpha,PGD2,11-Dehydroprostaglandin F2 alpha,11 Dehydroprostaglandin F2 alpha,11 Dehydroprostaglandin F2alpha,D2, Prostaglandin,F2 alpha, 11-Dehydroprostaglandin,F2alpha, 11-Dehydroprostaglandin,alpha, 11-Dehydroprostaglandin F2
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53

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