Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B

• Published in: Archives of toxicology Vol. 81; no. 5; pp. 347 - 351
• Main Authors: NAGASHIMA, Hitoshi, MAEDA-NAKAMURA, Kumiko, IWASHITA, Keiko, GOTO, Tetsuhisa
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2007; Springer Nature B.V
• Subjects: Anthracenes - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Imidazoles - pharmacology; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor Binding Protein 1 - metabolism; Insulin-Like Growth Factor Binding Protein 1 - secretion; Insulin-like growth factors; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mycotoxins - pharmacology; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pyridines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Time Factors; Toxicology; Tumors; Human; Stress-activated MAP kinase (SAPK); Enzyme; Secretion; Mitogen-activated protein kinase; Rubratoxin B; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Insulin-like growth factor binding protein-1 (IGFBP-1); In vitro; Stress; Insulin like growth factor binding protein 1; Digestive diseases
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-006-0162-5

The induction of insulin-like growth factor binding protein-1 (IGFBP-1) secretion by rubratoxin B was investigated using human hepatoma cell line HepG2; we also documented the involvement of stress-activated MAP kinases [c-Jun-N-terminal kinases (JNKs) and p38s] in this process. Rubratoxin B dramatically enhanced IGFBP-1 secretion, which peaked at a concentration of 40 microg/ml. The amount of IGFBP-1 mRNA increased with time and plateaued at 6 h. Compared with the amounts of IGFBP-1 secreted, the induction ratios of transcription were much smaller, indicating that IGFBP-1 secretion is regulated chiefly post-transcriptionally. The result of concomitant treatment with rubratoxin B and JNK inhibitor indicated that JNKs do not affect rubratoxin B-induced IGFBP-1 secretion. Alternatively, rubratoxin B-associated induction of IGFBP-1 secretion was marked in the absence of p38 inhibitor but attenuated in its presence. Therefore, p38s appear to stimulate rubratoxin B-induced IGFBP-1 secretion. Treatment with p38 inhibitor slightly increased the amount of rubratoxin B-induced IGFBP-1 mRNA. However this induction ratio was smaller than that of rubratoxin B-induced secretion, suggesting that p38s regulate IGFBP-1 secretion both transcriptionally and post-transcriptionally. In this study, we showed that rubratoxin B induces IGFBP-1 levels in HepG2 cells and p38s contribute to this process.