N-acetylcysteine downregulates vascular endothelial growth factor production by human keratinocytes in vitro.
The present study was designed to evaluate the action of various antioxidants including N-acetylcysteine (NAC) and the flavonoids resveratrol and quercetin on the production of VEGF by human keratinocytes (HKC). NAC, resveratrol, and quercetin dose-dependently suppressed the incorporation of 3H-thymidine into HKC. Values of median inhibitory concentration for NAC, resveratrol, and quercetin were 10 mM, 55 microM, and 15 microM, respectively (P < 0.01). RT-PCR demonstrated VEGF 121 and VEGF 206 expression in all HKC samples. HKC showed baseline expression and a progressive gradual time-dependent increase in VEGF secretion (510+/-75 pg/ml at 24 h), and EGF (2.5-100 ng/ml) enhanced the secretion of VEGF in a dose-dependent fashion. HKC were incubated with NAC (2.5-20 mM) for 2 h prior to the addition of EGF (5 ng/ml) or PMA (10 ng/ml), and a significant decrease (P < 0.01) was found after 24 h of incubation with 2.5 mM NAC. However, neither resveratrol nor quercetin reduced the synthesis of this cytokine. In summary we conclude that NAC and the flavonoid antioxidants resveratrol and quercetin inhibit HKC proliferation regardless of the stage of differentiation and that NAC significantly inhibits VEGF secretion in basal and EGF- or PMA-treated HKC.
Redondo
P
P
Department of Dermatology, University Clinic of Navarra, School of Medicine, Pamplona, Spain. predondo@unav.es
Jimenez
E
E
Perez
A
A
García-Foncillas
J
J
D000111:Acetylcysteine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008222:Lymphokines / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D000975:Antioxidants; D016228:Endothelial Growth Factors; D008222:Lymphokines; D013267:Stilbenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014316:Tritium; D011794:Quercetin; D000077185:Resveratrol; D013936:Thymidine; D000111:Acetylcysteine