title: Inhibitory effect of baicalein on IL-6-mediated signaling cascades in human myeloma cells.
abstract: Interleukin-6 (IL-6) is an important growth factor for myeloma cells. IL-6 promotes the survival and proliferation of multiple myeloma (MM) cells through the phosphorylated proteins, including STAT3, MAPK, and Akt. Chemical components that suppress the signaling proteins' phosphorylation have a potential role for MM therapy. We recently identified that baicalein, a component of Scutellaria radix, suppressed proliferation and induced apoptosis of myeloma cells by blocking IkappaB-alpha degradation followed by down-regulating IL-6 and XIAP gene expression. In the present study of four myeloma cell lines, namely U266, NOP2, AMO1, and ILKM2, we demonstrated that baicalein not only inhibited IL-6-mediated phosphorylation of signaling proteins, such as Jak, STAT3, MAPK, and Akt, but also inhibited the expression of their target genes, such as bcl-xl. Finally, baicalein facilitated myeloma cell proliferation inhibited by dexamethasone. In contrast, baicalin, another major flavonoid derived from Scutellaria radix, had no significant effect on IL-6-mediated protein phosphorylation. Baicalein had no effect on Akt phosphorylation induced by the insulin-like growth factor-1 (IGF-1) in NOP2 cells. Compared with PD98059, an MAPK inhibitor, baicalein exhibited a stronger inhibitory effect on Erk(1/2) phosphorylation. Our results demonstrate that baicalein is a potent inhibitor of protein phosphorylation induced by IL-6, and thus may be a useful agent for the treatment of MM.
authors.affiliation: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Shangqin
authors.initials: S
authors.lastname: Liu
authors.forename: Zi
authors.initials: Z
authors.lastname: Ma
authors.forename: Huili
authors.initials: H
authors.lastname: Cai
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Wenyu
authors.initials: W
authors.lastname: Rong
authors.forename: Michio
authors.initials: M
authors.lastname: Kawano
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; C494811:BCL2L1 protein, human; D044950:Flavanones; D005419:Flavonoids; C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051020:bcl-X Protein; C006680:baicalein; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one