Combinatorial Effects of Nonsteroidal Anti-inflammatory Drugs and Food Constituents on Production of Prostaglandin E2and Tumor Necrosis Factor-α in RAW264.7 Murine Macrophages
- 1 January 2003
- journal article
- Published by Taylor & Francis in Bioscience, Biotechnology, and Biochemistry
- Vol. 67 (5) , 1056-1062
- https://doi.org/10.1271/bbb.67.1056
Abstract
Combinatorial chemopreventive strategies, in contrast to those with individual agents, show potential in terms of potentially lower toxicity and higher efficacy. In this study, we combined several agents and examined their suppressive effects on the combined lipopolysaccharide (LPS)- and interferon(IFN)-gamma-induced formation of proinflammatory mediators, including prostaglandin (PG) E2 and tumor necrosis factor (TNF)-alpha, in RAW264.7 murine macrophages. The combinatorial effects of indomethacin/genistein (GEN) and aspirin/GEN were found to be synergistic for PGE2 suppression, while the nimesulide/GEN combination was antagonistic. Further, while (-)-epigallocatechin gallate (EGCG) alone increased LPS/IFM-gamma-induced production of PGE2 and TNF-alpha as well as cyclooxygenase-2 expression, the EGCG/GEN combination markedly suppressed these parameters. Our results suggest that certain chemopreventive agents act complexly and that, when used in combination, they affect the intracellular signaling pathways of the paired agents to exert additive, synergistic, or antagonistic effects.Keywords
This publication has 22 references indexed in Scilit:
- Molecular Mechanism of Viral HepatocarcinogenesisOncology, 2002
- Tumor necrosis factor-α induces the expression of DR6, a member of the TNF receptor family, through activation of NF-κBOncogene, 2001
- Involvement of ERK and Protein Tyrosine Phosphatase Signaling Pathways in EGCG-Induced Cyclooxygenase-2 Expression in Raw 264.7 CellsBiochemical and Biophysical Research Communications, 2001
- Cancer epidemiology in the last century and the next decadeNature, 2001
- Combinatorial chemoprevention of intestinal neoplasiaNature Medicine, 2000
- Multiagent chemopreventive agent combinationsJournal of Cellular Biochemistry, 2000
- Difluoromethylornithine in combination with tamoxifen in female rats: 13-week oral toxicity studyCancer Chemotherapy and Pharmacology, 1999
- Mice deficient in tumor necrosis factor-α are resistant to skin carcinogenesisNature Medicine, 1999
- Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in CombinationJapanese Journal of Cancer Research, 1998
- Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)Cell, 1996