Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells.
We found that quercetin, myricetin, quercetagetin, fisetin, (-)-epigallocatechin gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6 Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. The important structural features of flavonoids for cell transformation-inhibitory activity are 3'- and 4'-OH on the B-ring, 3-OH on the C-ring, C2=C3 double bond in the C-ring, and the phenylchromone (C6-C5-C6) skeleton in the flavonols, and the galloyl group in EGCG and theaflavins. Our results provide new insight into possible mechanisms of the anti-carcinogenic effects of flavonoids, and could help to provide a basis for the design of novel cancer chemopreventive agents.
Ichimatsu
Daisuke
D
Department of Hospital Pharmacy, School of Medicine, Kanazawa University, Kanazawa, Japan.
Nomura
Masaaki
M
Nakamura
Seiji
S
Moritani
Shuzo
S
Yokogawa
Koichi
K
Kobayashi
Shinjiro
S
Nishioka
Tatsuo
T
Miyamoto
Ken-ichi
K
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005419:Flavonoids / Q000627:therapeutic use*; D051379:Mice; D008956:Models, Chemical; D011485:Protein Binding; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000096:biosynthesis
D005419:Flavonoids; D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor