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Anti-proliferative Effects by Aqueous Extract of Cordyceps Militaris in Human Leukemic U937 Cells  

Park, Dong-Il (Department of Internal Medicine, College of Oriental Medicine, Dongeui University)
Seo, Sang-Ho (Department of Internal Medicine, College of Oriental Medicine, Dongeui University)
Choi, Yung-Hyun (Department f Biochmistry, College of Oriental Medicine, Dongeui University.Biomedical Research Center of Oriental Medicine)
Hong, Sang-Hoon (Department of Internal Medicine, College of Oriental Medicine, Dongeui University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.19, no.2, 2005 , pp. 452-458 More about this Journal
Abstract
Cordyceps militaris is a medicinal fungus, which has been used for patient suffering from cancer in Oriental medicine. It was reported previously that C. militaris extracts are capable of inhibiting tumor growth, however, the anti-poliferative effects of human cancer cells have not been poorly understood. In this study, to elucidate the growth inhibitory mechanisms of human cancer cells by treatment of aqueous extract of C. militaris (AECM) we investigated the anti-proliferative effects of AECM in human leukemia U937 cell line. AECM treatment inhibited the growth of U937 cells and induced the apoptotic cell death in a concentration-dependent manner, which was associated with morphological changes. We observed the up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) by p53-independent manner and activation of caspase-3 in AECM-treated U937 cells, however, the activity of caspase-9 was remained unchanged. Additionally, AECM treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1). Taken together, these findings suggest that AECM-induced inhibition of human leukemic cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.
Keywords
Cordyceps militaris; U937; p21; telomere;
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1 Sung, J.M., Lee, H.K., Choi, v.s, Kim, Y.O., Kim, S.H., Sung, G.H. Distribution and taxonomy of entomopathogenic fungal species from Korea. Kor J Mycol 25, 231-252, 1997.
2 Buenz, E.J., Bauer, B.A, Osmundson, T.W., Motley, T.J. The traditional Chinese medicine Cordyceps sinensis and its effects on apoptotic homeostasis. J Ethnopharmacol 96, 19-29, 2005.
3 Buenz, E.J., Weaver, J.G., Bauer, B.A., Chalpin, S.D., Badley, A.D. Cordyceps sinensis extracts do not prevent Pas-receptor and hydrogen peroxide-induced T-cell apoptosis. J Ethnopharmacol 90, 57-62, 2004.
4 Nakamura, K., Yamaguchi, Y., Kagota, S., Kwon, Y.M., Shinozuka, K., Kunitomo, M.. Inhibitory effect of Cordyceps sinensis on spontaneous liver metastasis of Lewis lung carcinoma and B16 melanoma cells in syngeneic mice. Jpn J Pharmacol 79, 335-341, 1999.
5 Kim, M.N., Oh, S.W., Lee, D.S., Ham, S.S. Antioxidative and antimutagenic effects of the ethanol extract from Cordycepes militaris. Kor J Posthavest Sci Technol 8, 109-117, 2001.
6 Yoo, H.S., Shin, J.W., Cho, J.H., Son, C.G., Lee, Y.W., Park, S.Y., Cho, C.K. Effects of Cordyceps militaris extract on angiogenesis and tumor growth. Acta Pharmacol Sin 25, 657-665, 2004
7 Harper, J.W. Cyclin dependent kinase inhibitors. Cancer Surv 29, 91-107, 1997.
8 Li, Y., Jenkins, C.W., Nichols, M.A., Xiong, Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene 9, 2261-2268, 1994.
9 Datto, M.B., Yu, Y., Wang, X.F. Functional analysis of the transforming growth factor $\beta$ responsive elements in the WAF1/Cip1/p21 promoter. J Biol Chem 270, 28623-28628, 1995.
10 Jiang, H., Lin, L Su, Z.Z., Collart, F.R., Huberman, E., Fisher, P.B. Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p2L WAF1/OP1, expression in the absence of p53. Oncogene 9, 3397-3406, 1994.
11 Reed, J.C. Bcl-2 family proteins. Oncogene, 17, 3225-3236, 1998.
12 Mathieu, N., Pirzio, L., Freulet-Marriere, M.A., Desmaze, C, Sabatier, L. Telomeres and chromosomal instability. Cell Mol Life Sci 61, 641-656, 2004.
13 Greenwood, M.J., Landsdorp, P.M. Telomeres, telornerase, and hematopoietic stem cell biology. Arch Med Res 34, 489-495, 2003.
14 Zeng, YX, EI-Deiry, vrs. Regulation of p21WAF1/CIP1 expression by p53-independent pathways. Oncogene 12, 1557-1564, 1996.
15 Nagata, S. Apopotosis by death factor. Cell 88, 355-365, 1997.
16 Chen, J.L., Greider, CW.. Telomerase RNA structure and function: implications for dyskeratosis congenita. Trends Biochem Sci 29, 183-192, 2004.
17 Evans, Y.G. Mutiple pathways to apoptosis. Cell Biol Int 17, 461-476, 1993.
18 Choi, Y.H., Kong, K.R., Kim, Y.A., Jung, K.O., Kil, J.H., Rhee, S.H., Park, K.Y. Induction of Bax and activation of caspases during $\beta$-sitosterol-mediated apoptosis in human colon cancer cells. Int J Oncol 23, 1657-1661, 2001
19 Homayoun, V., Sam, B. From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: The telomere loss/DNA damage model of cell aging. Exp Gerontol 31, 295-301, 1996.
20 Zimmermann, K.C., Bonzon, C, Green, D.R. The machinery of programmed cell death. Pharmacol Ther 92, 57-70, 2001.
21 Kaufmann, S.H., Desnoyers,S., Ottaviano, Y., Davidson, N. E., Poirier, G.G. Specific proteolytic cleavage of poly (ADPribose) polymerase: an early marker of chemotherapyinduced apoptosis. Cancer Res., 53, 3976-3985, 1993.
22 Sung, J.M., Yu, Y.B., Cha, D.Y. Mushroom science. Kyohaksa, Seoul, pp.569-570, 1998.
23 Kim, M.N., Cui, C.B., Lee, D.S., Ham, S.S. Cytotoxicity and antigenotoxic effect of Cordycepes militaris extracts. J Kor Soc Food Sci Nutr 30, 921-927, 2001.
24 Taylor, W.R., Stark, G.R. Regulation of the G2/M transition by p53. Oncogene 20, 1803-1815, 2001.
25 Chiarugi, V., Magneli, L., Cinelli, M., Basi, G. Apoptosis and the cell cycle. Cell Mol Biol Res, 40, 603-612, 1994.
26 Hong, S.H., Karn, C.W., Park, D.J. Induction of apoptotic cell death by an aqueous extract of Cordyceps militaris in A549 human lung carcinoma cells. Kor J Oriental Physiol Pathol 18, 1102-1106, 2004.
27 Howard, A, Pelc, S.R. Synthesis of deoxyribonucleic acid in normal and irradiated cells and its relation to chromosome breakage. Heredity 6, 261, 1953.
28 Lazebnik, Y.A., Kaufmann, S.H., Desnoyers, S., Poirier, G. G., Earnshaw, W.C. Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature, 371, 346-347, 1994.
29 Lee, H., Lee, Y., Park, T. Tumor growth inhibitory and imrnunomodulatory activities of Cordycepes militaris water extracts in ICR mice bearing Sarcoma-180 solid tumor. J Kor Soc Food Sci Nutr 33, 59-65, 2004.
30 Choi. Y.H., Lee, W.H., Park, K.Y., Zhang, L. p53-independent induction of p21 (WAF1/CIP1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn J Cancer Res 91, 164-173, 2000.
31 Shahed, AR, Kim, S.I., Shoskes, D.A. Down-regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischcmia/reperfusion. Transplant Proc 33, 2986-2987, 2001.
32 Xiong, Y., Hannon, G.J., Zhang, H, Casso, D., Kobayashi, R., Beach, D. p21 is a universal inhibitor of cydin kinases. Nature 366, 701-704, 1993.
33 Minshull, J., Pines, J., Golsteyn, R, Standart, N., Mackie, S., Colman, A., Blow, J., Ruderman, JV., Wu, M., Hunt, T. The role of cyclin synthesis, modification and destruction in the control of cell division. J Cell Sci Suppl 12, 77-97, 1989.
34 Liebertha. I W., Koh, J.S, Levine, J.S. Necrosis and apoptosis in acute renal failure. Semin Nephrol 18, 505-518, 1998.