title: A novel ginseng saponin metabolite induces apoptosis and down-regulates fibroblast growth factor receptor 3 in myeloma cells.
abstract: Ginseng (the root of Panax ginseng C.A. Meyer, Araliaceae) has been used as a crude drug taken orally for preventive and therapeutic purposes in Asian countries as a traditional medicine. In the current study, we have investigated the antitumor effect of a novel ginseng protopanaxadiol saponin bacterial metabolic derivative, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901), in eight human myeloma cell lines. IH-901 inhibited the proliferation of all myeloma cell lines examined. Despite the fibroblast growth factor receptor 3 (FGFR3) overexpression due to a chromosomal translocation t(4;14)(q16.3;q32.3) in KMS-11 myeloma cells, IH-901 induced apoptosis in a dose- and time-dependent way in this cell line. Treatment of KMS-11 with IH-901 resulted in the formation of internucleosomal DNA fragments, poly (ADP-ribose) polymerase cleavage, and the activation of caspase-3. IH-901 also caused the down-regulation of FGFR3 mRNA and protein expression and inhibited ERK activity in KMS-11 cells. Our results demonstrate that IH-901 induces apoptosis and inhibits FGFR3 expression and signaling in KMS-11 cells, suggesting candidacy for the chemoprevention and the treatment of myeloma.
authors.affiliation: National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Choi
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Jong
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Seongwon
authors.initials: S
authors.lastname: Choi
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Namba
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D016923:Cell Death; D002455:Cell Division; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D005894:Panax / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry*; D015398:Signal Transduction; D013997:Time Factors; D014178:Translocation, Genetic
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D012503:Saponins; D012313:RNA; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3