title: Effects of Hydroxy Groups in the A-Ring on the Anti-proteasome Activity of Flavone.
abstract: The ubiquitin-proteasome pathway plays an important role in regulating apoptosis and the cell cycle. Recently, proteasome inhibitors have been shown to have antitumor effects and have been used in anticancer therapy for several cancers such as multiple myeloma. Although some flavones, such as apigenin, chrysin and luteolin, have a specific role in the inhibition of proteasome activity and induced apoptosis in some reports, these findings did not address all flavone types. To further investigate the proteasome-inhibitory mechanism of flavonoids, we examined the inhibitory activity of 5,6,7-trihydroxyflavone, baicalein and 5,6,7,4'-tetrahydroxyflavone, scutellarein on extracted proteasomes from mice and cancer cells. Unlike the other flavones, baicalein and scutellarein did not inhibit proteasome activity or accumulate levels of ubiquitinated proteins. These results indicate that flavones with hydroxy groups at positions 5, 6 and 7 of the A-ring lack the anti-proteasome function.
authors: Department of Biochemistry, Hamamatsu University School of Medicine.
authors: Kasumi
authors: K
authors: Nakamura
authors: Jia-Hua
authors: JH
authors: Yang
authors: Eiji
authors: E
authors: Sato
authors: Naoyuki
authors: N
authors: Miura
authors: Yi-Xin
authors: YX
authors: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D047309:Flavones; D010936:Plant Extracts; D061988:Proteasome Inhibitors; C006680:baicalein; D047310:Apigenin; D046988:Proteasome Endopeptidase Complex; C458179:scutellarein; C043562:flavone