Abstract
Previous results suggested that the cyclooxygenase-2 pathway and prostaglandins might modulate 3T6 fibroblast growth. This study shows the effect of resveratrol on the main elements of arachidonic acid (AA) cascade and 3T6 fibroblast growth. The polyphenol reduced the reactive oxygen species production stimulated by fetal calf serum or platelet-derived growth factor, as well as phospholipase A2activity translocation and the subsequent [3H]AA release and prostaglandin E2 synthesis induced by these growth factors. A Western blot analysis demonstrated that cyclooxygenase-2 induction stimulated by fetal calf serum or platelet-derived growth factor was inhibited by resveratrol. The effects of resveratrol on AA cascade were correlated with an impairment of 3T6 fibroblast proliferation and DNA synthesis. These results suggest that reactive oxygen species and AA, and/or prostaglandins such as prostaglandin E2 might be involved in the control of 3T6 fibroblast growth by resveratrol.
Footnotes
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Send reprint requests to: Dr. Juan J. Moreno, Departamento de Fisiologı́a, Facultad de Farmacia, Universidad de Barcelona, Avda. Joan XXIII s/n, E-08028 Barcelona, Spain. E-mail:moreno{at}farmacia.far.ub.es
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↵1 This study was supported by Spanish Ministry of Education Grants PM97-0110 and PM98-0191.
- Abbreviations:
- AA
- arachidonic acid
- PLA2
- phospholipase A2
- COX
- cyclooxygenase
- PG
- prostaglandin
- FCS
- fetal calf serum
- PDGF
- platelet-derived growth factor
- ROS
- reactive oxygenated species
- DCFL-DA
- 2′,7′-dichlorofluorescein diacetate
- Received December 3, 1999.
- Accepted April 10, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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