title: Sanggenon C decreases tumor cell viability associated with proteasome inhibition.
abstract: Several flavonoids have been reported to be proteasome inhibitors, but whether prenylated flavonoids are able to inhibit proteasome function remains unknown. We report for the first time that Sanggenon C, a natural prenylated flavonoid, inhibits tumor cellular proteasomal activity and cell viability. We found that (1) Sanggenon C inhibited tumor cell viability and induced cell cycle arrest at G0/G1 phase; (2) Sanggenon C inhibited the chymotrypsin-like activity of purified human 20S proteasome and 26S proteasome in H22 cell lysate, and Sanggenon C was able to dose-dependently accumulate ubiquitinated proteins and proteasome substrate protein p27; (3) Sanggenon C-induced proteasome inhibition occurred prior to cell death in murine H22 and P388 cell lines; (4) Sanggenon C induced death of human K562 cancer cells and primary cells isolated from leukemic patients. We conclude that Sanggenon C inhibits tumor cell viability via induction of cell cycle arrest and cell death, which is associated with its ability to inhibit the proteasome function and that proteasome inhibition by Sanggenon C at least partially contributes to the observed tumor cell growth-inhibitory activity.
authors.affiliation: Department of Pathophysiology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Guangzhou Medical College, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Huang
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Lu
authors.forename: Shujue
authors.initials: S
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Lian
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Dong
authors.forename: Canguo
authors.initials: C
authors.lastname: Zhao
authors.forename: Haiping
authors.initials: H
authors.lastname: Guo
authors.forename: Change
authors.initials: C
authors.lastname: Zhang
authors.forename: Changshan
authors.initials: C
authors.lastname: Yang
authors.forename: Guanmei
authors.initials: G
authors.lastname: Wen
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Li
authors.forename: Lixia
authors.initials: L
authors.lastname: Guan
authors.forename: Chunjiao
authors.initials: C
authors.lastname: Liu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Qing Ping
authors.initials: QP
authors.lastname: Dou
authors.forename: Jinbao
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D051379:Mice
chemical_list: D001572:Benzofurans; D002867:Chromones; C477157:sanggenone C