NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines.

Abstract

Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time- and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX-2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS-398 in hepatocellular carcinoma cell lines.

• Authors: Jidong Cheng, Hiroyasu Imanishi, Yoshiki Amuro, Toshikazu Hada
• Journal: International journal of cancer (Int J Cancer) Vol. 99 Issue 5 Pg. 755-61 (Jun 10 2002) ISSN: 0020-7136 [Print] United States
• PMID: 12115513 (Publication Type: Journal Article)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Membrane Proteins
• Nitrobenzenes
• Proliferating Cell Nuclear Antigen
• RNA, Messenger
• Sulfonamides
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• 6-Ketoprostaglandin F1 alpha
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• 6-Ketoprostaglandin F1 alpha (biosynthesis)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (enzymology, pathology, prevention & control)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (biosynthesis)
• G1 Phase (drug effects)
• Humans
• Isoenzymes (analysis, antagonists & inhibitors, genetics)
• Liver Neoplasms (enzymology, pathology, prevention & control)
• Membrane Proteins
• Nitrobenzenes (pharmacology)
• Proliferating Cell Nuclear Antigen (analysis)
• Prostaglandin-Endoperoxide Synthases (analysis, genetics)
• RNA, Messenger (analysis)
• Resting Phase, Cell Cycle (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• S Phase (drug effects)
• Sulfonamides (pharmacology)
• Tumor Cells, Cultured