Quercetin induces gadd45 expression through a p53-independent pathway.
Quercetin, a kind of flavonoid, is found in edible fruits and vegetables and has anti-tumorigenic activity. However, the mechanism of activity has not been elucidated. We show for the first time that gadd45 is a molecular target of quercetin, which inhibits growth of human cervical cancer HeLa cells. Apoptosis was detected in HeLa cells treated with quercetin. At the concentration inducing apoptosis, quercetin also increased gadd45 expression at the mRNA and protein level, however, the 5'-promoter region of the gadd45 gene was not activated by quercetin. Since gadd45 is known to be a downstream gene of the tumor suppressor p53, we examined whether or not quercetin regulates gadd45 induction via a p53 pathway. Quercetin did not activate transcription through p53-binding sites in HeLa cells, although it up-regulated gadd45 in p53-inactivated tumor cells. These results indicate that quercetin induces gadd45 expression in a p53-independent manner.
Yoshida
Tatsushi
T
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Maeda
Ayaka
A
Horinaka
Mano
M
Shiraishi
Takumi
T
Nakata
Susumu
S
Wakada
Miki
M
Yogosawa
Shingo
S
Sakai
Toshiyuki
T
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011794:Quercetin; D012333:RNA, Messenger; C439070:GADD45A protein, human; D000097642:GADD45 Proteins