title: Herbal cocktail ka-mi-kae-kyuk-tang stimulates mouse bone marrow stem cell hematopoiesis and janus-activated kinase 2/signal transducer and activator of transcription 5 pathway.
abstract: Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail. Our collaborative team has shown that it has potent anti-angiogenic, anti-cancer and anti-metastatic activities in vivo without observable side effects. We have documented evidence for KMKKT to alleviate drug-induced hematotoxicity in vivo. In the present study, we investigated the mechanistic and signaling events through which KMKKT enhances hematopoiesis, using hematopoietic stem cells (HSCs) isolated from the bone marrow of 8-12 week-old C57BL/6 mice. Our results show that KMKKT significantly increased the expression of the hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in HSCs. KMKKT also increased the expression of c-Kit, a cytokine receptor expressed in HSCs. In addition, KMKKT enhanced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), and increased the binding activity of STAT5 to gamma interferon activated sites (GAS) that mediate JAK2 downstream signaling. Furthermore, we found that KMKKT significantly enhanced the growth rate of colony-forming unit granulocyte erythrocyte monocyte macrophages (CFU-GEMM) and burst forming unit erythroid (BFU-E) of mouse HSCs (mHSCs) stimulated by IL-3/EPO. Overall, our results demonstrated that KMKKT alleviated drug-induced side effects through enhanced hematopoiesis, at least in part through cytokine-mediated JAK2/STAT5 signaling.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Inweon
authors.initials: I
authors.lastname: Seo
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Wonil
authors.initials: W
authors.lastname: Koh
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Tae-Rin
authors.initials: TR
authors.lastname: Kwon
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ihn
authors.initials: I
authors.lastname: Han
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Sun-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Jung
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lu
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D007377:Interleukin-3; D010936:Plant Extracts; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor; D053614:Janus Kinase 2