Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest.

Abstract

AIM:

To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7).

METHODS:

HepG2 and Huh7 cells were treated with NS-398. Its effects on cell viability, cell proliferation, cell cycles, and gene expression were respectively evaluated by water-soluble tetrazolium salt (WST-1) assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis, and Western blotting, with dimethyl sulfoxide (DMSO) as positive control.

RESULTS:

NS-398 showed dose- and time-dependent growth-inhibitory effects on the two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2 and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose-independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of apoptosis was observed in two cell lines.

CONCLUSION:

NS-398 reduces cell proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX-2 inhibitors may have potent chemoprevention effects on human hepatocellular carcinoma.

• Authors: Ji Yeon Baek, Wonhee Hur, Jin Sang Wang, Si Hyun Bae, Seung Kew Yoon
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 13 Issue 8 Pg. 1175-81 (Feb 28 2007) ISSN: 1007-9327 [Print] United States
• PMID: 17451196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Nitrobenzenes
• Sulfonamides
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• Cyclooxygenase 2

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology, therapeutic use)
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Nitrobenzenes (pharmacology, therapeutic use)
• Sulfonamides (pharmacology, therapeutic use)