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

Jeong Eun Lee, Inweon Seo, Soo Jin Jeong, Wonil Koh, Ji Hoon Jung, Tae Rin Kwon, Hyo Jung Lee, Ihn Han, Hyo Jeong Lee, Eun Ok Lee, Sun Hyung Kim, Hee Jae Jung, Junxuan Lu, Sung Hoon Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 812 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.

Original languageEnglish (US)
Pages (from-to)1235-1252
Number of pages18
JournalAmerican Journal of Chinese Medicine
Volume39
Issue number6
DOIs
StatePublished - Nov 18 2011

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STAT5 Transcription Factor
Janus Kinase 2
Hematopoiesis
Hematopoietic Stem Cells
Bone Marrow Cells
Stem Cells
Interleukin-3
Erythropoietin
Cytokines
Thrombopoietin
Erythroid Precursor Cells
Cytokine Receptors
Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Drug-Related Side Effects and Adverse Reactions
Inbred C57BL Mouse
Granulocytes
Interferon-gamma
Monocytes
Erythrocytes

All Science Journal Classification (ASJC) codes

  • Complementary and alternative medicine

Cite this

Lee, Jeong Eun ; Seo, Inweon ; Jeong, Soo Jin ; Koh, Wonil ; Jung, Ji Hoon ; Kwon, Tae Rin ; Lee, Hyo Jung ; Han, Ihn ; Lee, Hyo Jeong ; Lee, Eun Ok ; Kim, Sun Hyung ; Jung, Hee Jae ; Lu, Junxuan ; Kim, Sung Hoon. / 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. In: American Journal of Chinese Medicine. 2011 ; Vol. 39, No. 6. pp. 1235-1252.
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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 812 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.",
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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. / Lee, Jeong Eun; Seo, Inweon; Jeong, Soo Jin; Koh, Wonil; Jung, Ji Hoon; Kwon, Tae Rin; Lee, Hyo Jung; Han, Ihn; Lee, Hyo Jeong; Lee, Eun Ok; Kim, Sun Hyung; Jung, Hee Jae; Lu, Junxuan; Kim, Sung Hoon.

In: American Journal of Chinese Medicine, Vol. 39, No. 6, 18.11.2011, p. 1235-1252.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Lee, Jeong Eun

AU - Seo, Inweon

AU - Jeong, Soo Jin

AU - Koh, Wonil

AU - Jung, Ji Hoon

AU - Kwon, Tae Rin

AU - Lee, Hyo Jung

AU - Han, Ihn

AU - Lee, Hyo Jeong

AU - Lee, Eun Ok

AU - Kim, Sun Hyung

AU - Jung, Hee Jae

AU - Lu, Junxuan

AU - Kim, Sung Hoon

PY - 2011/11/18

Y1 - 2011/11/18

N2 - 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 812 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.

AB - 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 812 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.

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