title: Suppression of U937 human monocytic leukemia cell growth by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., via induction of Cdk inhibitor p16 and down-regulation of pRB phosphorylation.
abstract: Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, the mechanisms of which however, are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which dideoxypetrosynol A exerts its anti-proliferative action in cultured human monocytic leukemia U937 cells. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest in the cell cycle, the effects of which were associated with up-regulation of cyclin D1 and down-regulation of cyclin E, in a concentration-dependent manner without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and transcription factor E2F-1. Overall, our results demonstrate a combined mechanism involving the inhibition of pRB phosphorylation and induction of p16 as targets for dideoxypetrosynol A, may explain some of its anti-cancer effects.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Gi Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Gun Do
authors.initials: GD
authors.lastname: Kim
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Lee
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Cheong
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Song-Ja
authors.initials: SJ
authors.lastname: Bae
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives / Q000737:chemistry; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000494:pharmacology; D050684:E2F Transcription Factors / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology*; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry; D053279:Polyynes; D011161:Porifera; D016160:Retinoblastoma Protein / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000480:Alkynes; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050684:E2F Transcription Factors; D005233:Fatty Alcohols; D011108:Polymers; D016160:Retinoblastoma Protein; C499970:dideoxypetrosynol A; D053279:Polyynes; D000114:Acetylene