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

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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.

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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All Science Journal Classification (ASJC) codes

  • Complementary and alternative medicine

Cite this

Lee, J. E., Seo, I., Jeong, S. J., Koh, W., Jung, J. H., Kwon, T. R., Lee, H. J., Han, I., Lee, H. J., Lee, E. O., Kim, S. H., Jung, H. J., Lu, J., & Kim, S. H. (2011). 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. American Journal of Chinese Medicine, 39(6), 1235-1252. https://doi.org/10.1142/S0192415X11009524