An Oriental Herbal Cocktail
An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis
Hyo-Jeong Lee1,2, Eun-Ok Lee1, Yun-Hee Rhee1, Kyoo Seok Ahn1, Guang-Xun Li2, Cheng Jiang2, Junxuan Lü2 and Sung-Hoon Kim1,*
1 Laboratory of Angiogenesis and Chemoprevention, College of Oriental Medicine Kyunghee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea
2 Hormel Institute, University of Minnesota Austin, MN 55912, USA
*To whom correspondence should be addressed Email: sungkim7@khu.ac.kr
Rigorous and systematic pre-clinical studies are necessary and essential to establish the efficacy and safety of Oriental herbs and formulas in order to transform traditional herbal practices into evidence-based medicine.
Here we evaluated the anti-cancer activities of the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT), a formula of ten Oriental herbs, with a battery of in vitro and in vivo mechanism-based biomarkers involving angiogenesis, apoptosis and metastasis.
The results show that KMKKT suppressed the vascular endothelial responses by inhibiting basic fibroblast growth factor (bFGF)-induced ERK1/2 phosphorylation, cell migration as well as tube formation in the human umbilical vein endothelial cell model, and decreased the hypoxia-induced HIF1 and vascular epithelial growth factor (VEGF) expression in the mouse Lewis lung carcinoma (LLC) cells in vitro, and inhibited the bFGF-induced angiogenesis in chick chorioallantoic membrane model, and in the Matrigel plugs in mice.
Intraperitoneal delivery of KMKKT potently inhibited the growth of the subcutaneously inoculated LLC cells in syngenic mice. In addition, KMKKT inhibited the invasion ability of the mouse colon 26-L5 cancer cells in vitro and decreased their formation of liver metastasis when intraportally inoculated in syngenic mice.
Furthermore, KMKKT suppressed the growth of the human PC-3 prostate cancer xenografts in athymic nude mice and averted the cancer-related body weight loss. The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis.
Together, our data support broad-spectra in vivo anti-cancer activities of KMKKT targeting angiogenesis, apoptosis and metastasis without any adverse effect on the body weight. This formula merits serious consideration for further evaluation for the chemoprevention and treatment of cancers of multiple organ sites.
Carcinogenesis 2006 27(12):2455-2463; doi:10.1093/carcin/bgl104
Immunopharmacol Immunotoxicol. 2011 Dec;33(4):682-90. doi: 10.3109/08923973.2011.560159. Epub 2011 Mar 11.
Ka-mi-kae-kyuk-tang Oriental Herbal Cocktail Attenuates Cyclophosphamide-Induced Leukopenia Side Effects in Mouse
Inweon Seo 1, Seung-Hyung Kim, Jeong-Eun Lee, Soo-Jin Jeong, Young Chul Kim, Kyoo Seok Ahn, Junxuan Lu, Sung-Hoon Kim PMID: 21395405
Abstract
Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail and has been shown to have potent antiangiogenic, anticancer, and antimetastatic activities in preclinical animal models without observable side effects. We previously found that in prostate cancer xenograft experiments, treating tumor-bearing mice with KMKKT alleviated the body weight loss toward the end of the study, suggesting a general health-promoting activity. We investigated whether KMKKT alleviated cancer chemotherapy drug-induced leukopenia and other hematotoxicity in vivo using a mouse model. KMKKT was given once daily orally for 10 days to the mice before they were given cyclophosphamide (CPA) daily injection for 4 days.
KMKKT blunted CPA-induced decrease in red blood cells, hemoglobin content, and the total white blood cell/leukocyte counts. Examination of the multiple organ sites involved in hematopoiesis, and lymphocyte differentiation and maturation showed the attenuated changes induced by CPA in each and every type of cells examined. Particularly, some of the cell types are fully restored in the bone marrow and even overstimulated in the Sca-1(+), CD117(+), or Sca1(+)/CD117(+) and CD34(+)/CD117(+) stem cells, supporting a role of KMKKT to stimulate hematopoietic stem cell (HSC) signaling to compensate for CPA-induced destruction of leukocytes and other cell types.
Taken together, KMKKT might be a safe and effective herbal complementary and alternative medicine (CAM) modality to alleviate cancer drug-induced hematological side effects in addition to its anticancer activities. Preclinical investigations with other chemo- and radiation modalities are warranted to support planning translation consideration for human patients.
Hyo-Jeong Lee1,2, Eun-Ok Lee1, Yun-Hee Rhee1, Kyoo Seok Ahn1, Guang-Xun Li2, Cheng Jiang2, Junxuan Lü2 and Sung-Hoon Kim1,*
1 Laboratory of Angiogenesis and Chemoprevention, College of Oriental Medicine Kyunghee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea
2 Hormel Institute, University of Minnesota Austin, MN 55912, USA
*To whom correspondence should be addressed Email: sungkim7@khu.ac.kr
Rigorous and systematic pre-clinical studies are necessary and essential to establish the efficacy and safety of Oriental herbs and formulas in order to transform traditional herbal practices into evidence-based medicine.
Here we evaluated the anti-cancer activities of the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT), a formula of ten Oriental herbs, with a battery of in vitro and in vivo mechanism-based biomarkers involving angiogenesis, apoptosis and metastasis.
The results show that KMKKT suppressed the vascular endothelial responses by inhibiting basic fibroblast growth factor (bFGF)-induced ERK1/2 phosphorylation, cell migration as well as tube formation in the human umbilical vein endothelial cell model, and decreased the hypoxia-induced HIF1 and vascular epithelial growth factor (VEGF) expression in the mouse Lewis lung carcinoma (LLC) cells in vitro, and inhibited the bFGF-induced angiogenesis in chick chorioallantoic membrane model, and in the Matrigel plugs in mice.
Intraperitoneal delivery of KMKKT potently inhibited the growth of the subcutaneously inoculated LLC cells in syngenic mice. In addition, KMKKT inhibited the invasion ability of the mouse colon 26-L5 cancer cells in vitro and decreased their formation of liver metastasis when intraportally inoculated in syngenic mice.
Furthermore, KMKKT suppressed the growth of the human PC-3 prostate cancer xenografts in athymic nude mice and averted the cancer-related body weight loss. The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis.
Together, our data support broad-spectra in vivo anti-cancer activities of KMKKT targeting angiogenesis, apoptosis and metastasis without any adverse effect on the body weight. This formula merits serious consideration for further evaluation for the chemoprevention and treatment of cancers of multiple organ sites.
Carcinogenesis 2006 27(12):2455-2463; doi:10.1093/carcin/bgl104
Immunopharmacol Immunotoxicol. 2011 Dec;33(4):682-90. doi: 10.3109/08923973.2011.560159. Epub 2011 Mar 11.
Ka-mi-kae-kyuk-tang Oriental Herbal Cocktail Attenuates Cyclophosphamide-Induced Leukopenia Side Effects in Mouse
Inweon Seo 1, Seung-Hyung Kim, Jeong-Eun Lee, Soo-Jin Jeong, Young Chul Kim, Kyoo Seok Ahn, Junxuan Lu, Sung-Hoon Kim PMID: 21395405
Abstract
Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail and has been shown to have potent antiangiogenic, anticancer, and antimetastatic activities in preclinical animal models without observable side effects. We previously found that in prostate cancer xenograft experiments, treating tumor-bearing mice with KMKKT alleviated the body weight loss toward the end of the study, suggesting a general health-promoting activity. We investigated whether KMKKT alleviated cancer chemotherapy drug-induced leukopenia and other hematotoxicity in vivo using a mouse model. KMKKT was given once daily orally for 10 days to the mice before they were given cyclophosphamide (CPA) daily injection for 4 days.
KMKKT blunted CPA-induced decrease in red blood cells, hemoglobin content, and the total white blood cell/leukocyte counts. Examination of the multiple organ sites involved in hematopoiesis, and lymphocyte differentiation and maturation showed the attenuated changes induced by CPA in each and every type of cells examined. Particularly, some of the cell types are fully restored in the bone marrow and even overstimulated in the Sca-1(+), CD117(+), or Sca1(+)/CD117(+) and CD34(+)/CD117(+) stem cells, supporting a role of KMKKT to stimulate hematopoietic stem cell (HSC) signaling to compensate for CPA-induced destruction of leukocytes and other cell types.
Taken together, KMKKT might be a safe and effective herbal complementary and alternative medicine (CAM) modality to alleviate cancer drug-induced hematological side effects in addition to its anticancer activities. Preclinical investigations with other chemo- and radiation modalities are warranted to support planning translation consideration for human patients.
