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We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadioltype ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase (CDK) inhibitor p27<SUP>Kip1</SUP> as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a timedependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in tumor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence- labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumorinduced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.
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참고문헌 (41)
참고문헌 신청
1. [학술지(정기간행물)] - / 1975 / Effect of ginseng saponins on cholesterol metabolism The level and the synthesis of serum and liver cholesterol in rats treated with ginsenosides : 1009 ~ 1016
2. [학술지(정기간행물)] - / 1976 / Stimulation of serum protein synthesis in ginsenoside treated rat (zaki) : 2818 ~ 2824
3. [학술지(정기간행물)] - / 1990 / Induction of neutrophil accumulation by red ginseng eth (pharma) : 315 ~ 318
4. [학술지(정기간행물)] - / 1990 / Immunomodulatory effects of two extracts of Panax ginseng C : 537 ~ 542
5. [학술지(정기간행물)] - / 1992 / Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine immu (l) : 1519 ~ 1525
2. [학술지(정기간행물)] - / 1976 / Stimulation of serum protein synthesis in ginsenoside treated rat (zaki) : 2818 ~ 2824
3. [학술지(정기간행물)] - / 1990 / Induction of neutrophil accumulation by red ginseng eth (pharma) : 315 ~ 318
4. [학술지(정기간행물)] - / 1990 / Immunomodulatory effects of two extracts of Panax ginseng C : 537 ~ 542
5. [학술지(정기간행물)] - / 1992 / Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine immu (l) : 1519 ~ 1525
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