title: The flavonoid apigenin downregulates CDK1 by directly targeting ribosomal protein S9.
abstract: Flavonoids have been reported to inhibit tumor growth by causing cell cycle arrest. However, little is known about the direct targets of flavonoids in tumor growth inhibition. In the present study, we developed a novel method using magnetic FG beads to purify flavonoid-binding proteins, and identified ribosomal protein S9 (RPS9) as a binding partner of the flavonoid apigenin. Similar to treatment with apigenin, knockdown of RPS9 inhibited the growth of human colon cancer cells at the G2/M phase by downregulating cyclin-dependent kinase 1 (CDK1) expression at the promoter level. Furthermore, knockdown of RPS9 suppressed G2/M arrest caused by apigenin. These results suggest that apigenin induces G2/M arrest at least partially by directly binding and inhibiting RPS9 which enhances CDK1 expression. We therefore raise the possibility that identification of the direct targets of flavonoids may contribute to the discovery of novel molecular mechanisms governing tumor growth.
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Iizumi
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Oishi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Wakana
authors.initials: W
authors.lastname: Goi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
mesh_terms: D047310:Apigenin / Q000378:metabolism / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; D047310:Apigenin; D016203:CDC2 Protein Kinase