Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upregulation of p21(WAF1CIP1) mRNA and protein expression during liver regeneration after partial hepatectomy

Quercetin, a widely distributed bioflavonoid, inhibited DNA synthesis in re generating liver after partial hepatectomy. This inhibition was accompanied by apoptosis, evidenced by in situ end-labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was detected as early as 2 h after injection. Northern blot analysis revealed that quercetin indu ced the increases in c-fos and p21(WAFICIPI) mRNA levels within 2 h. The ex pression of p21 protein was also enhanced, while p53 mRNA and protein level s were not affected by quercetin. These results suggest that quercetin-indu ced apoptosis is associated with the increase in c-fos mRNA level and the u pregulation of p21 mRNA and protein expression, probably in a p53-independe nt pathway. (C) 1999 Elsevier Science B.V. All rights reserved.