title: Inhibition of JAK1/STAT3 signaling mediates compound K-induced apoptosis in human multiple myeloma U266 cells.
abstract: Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis. Here, the role of STAT3 pathway in the antitumor activity of an active ginseng saponin metabolite compound K (CK) was investigated in human multiple myeloma U266 cells. CK increased the cytotoxicity, accumulated the sub-G1 DNA population, cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-3 in U266 cells. Interestingly, CK inhibited phosphorylation of STAT3 and its upstream activators, the Janus activated kinase 1 (JAK1), but not JAK2. Furthermore, CK enhanced the expression of protein tyrosine phosphatase (PTP) SHP-1, but not PTEN. Additionally, CK down-regulated STAT3 target genes bcl-x(L), bcl-2, survivin, cyclin E and cyclin D1. Conversely, PTP inhibitor pervanadate reversed CK-mediated STAT3 inactivation and cleavages of caspase-3 and PARP. Overall, our findings demonstrate that JAK1/STAT3 signaling mediates CK-induced apoptosis in U266 cells and also suggest the chemopreventive potential of CK for treatment of multiple myeloma.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Park
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Song
authors.forename: Minseok
authors.initials: M
authors.lastname: Kim
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Kyoo Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005894:Panax; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D053613:Janus Kinase 1; D011065:Poly(ADP-ribose) Polymerases; D017027:Protein Tyrosine Phosphatases; D050796:STAT3 Transcription Factor; D014638:Vanadates; C494086:STAT3 protein, human; C076715:pervanadate; C112772:ginsenoside compound K; C507904:JAK1 protein, human