A novel ginseng saponin metabolite induces apoptosis and down-regulates fibroblast growth factor receptor 3 in myeloma cells.
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.
Choi
Hyun Ho
HH
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jong
Hyun-Soon
HS
Park
Jung-Hyun
JH
Choi
Seongwon
S
Lee
Jung Weon
JW
Kim
Tae-You
TY
Otsuki
Takemi
T
Namba
Masayoshi
M
Bang
Yung-Jue
YJ
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
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