1. Pharmacol Toxicol. 2003 Dec;93(6):275-83.
In vitro induction of differentiation by ginsenoside Rh2 in SMMC-7721 hepatocarcinoma cell line.
Zeng XL, Tu ZG.Laboratory Medicine of An-Zhen Hospital, Capital University of Medical Sciences, Beijing 100029, China.
The aim of this study was to investigate the effects of ginsenoside Rh(2) (G-Rh(2)) on differentiation of SMMC-7721 hepatocarcinoma cell line in culture. We studied G-Rh(2)-induced differentiation of SMMC-7721 cells through cell proliferation, cell morphology, ultrastructure, cell cycle, cell function and metabolism. The proliferation of treated cells was inhibited, the morphology and ultrastructure seemed normal, the secretory amount and expression of alpha-foetoprotein, and the specific activity of gamma-glutamyl transpeptidase, and heat-resistant alkaline phosphatase were all significantly decreased, the secretory amount of albumin and alkaline phosphatase activity were remarkably increased, and the cell was arrested at the G(1)/G(0) phase. Furthermore, G-Rh(2) induced elevated expression of the cyclin-dependent kinase inhibitor p21(WAF1) and p16(INK4a), and declined expressions of cyclin D1 and cyclin E. In addition, G-Rh(2) almost completely inhibited telomerase activity, as measured by polymerase chain reaction-based telo(말단)meric repeat amplification protocol coupled with enzyme-linked immune sorbent assay, and human telomerase reverse transcriptase mRNA. Based on these data, it is suggested that G-Rh(2) could induce cell differentiation tending to normal and effectively reduce telomerase activity with affecting transcription levels of human telomerase reverse transcriptase, paralleling the induction of cell differentiation.
Rh2는 의 전사 수준에 영향을 미치는 인간의 telomerase (mRNA의 전사효소를 전화시킨다)작용을 효과적으로 감소시켜 세포 분화를 유도하는 것으로 추측된다.
2. Ai Zheng. 2004 Aug;23(8):879-84
[Induction of differentiation by ginsenoside Rh2 in hepatocarcinoma cell SMMC-7721]
[Article in Chinese]Zeng XL, Tu ZG.Clinical Laboratory of Anzhen Hospital,Capital University of Medical Sciences, Beijing, 100029, PR China.
BACKGROUND & OBJECTIVE: Up to now, searching for non-toxic and natural origin substances that induced the differentiation of cancer cells is a key for anticancer therapy. Ginseng is one of the most widely used natural tonics in oriental countries for thousands of years and has been reported to have various biological effects. Ginsenosides are thought to be the major effective ingredients in ginseng. Among them, ginsenoside Rh2(G-Rh2) has been suggested to have a cell-growth suppressive effect on various cancer cells, but the mechanism is unclear. This study was to investigate the induced differentiative effects of G-Rh2 on SMMC-7721 hepatocarcinoma cells. METHODS: Effects of G-Rh2 on cell viability was analyzed by MTT assay. Cell morphology was examined by a light and electronic microscope. Alpha-fetoprotein (AFP) in plasma was determined qualitatively and quantitatively with immunohistochemistry and ELISA. The specific activities of alkaline phosphatase (ALP) and heat-resistant ALP in plasma were assayed by ALP kit based on Bessey method. The specific activity of gamma-glutamyltranspeptidase (gamma-GT) was measured with gamma-GT kit.The secretory amount of AFP or albumin was detected with radioimmunoassay kit. RESULTS: G-Rh2 inhibited the proliferation of SMMC-7721 cells in dose and time-dependent manners. The inhibition rate was 50.87% after 6-day treatment with 10 microg/ml G-Rh2 while 46.84% after 4-day treatment with 20 microg/ml G-Rh2. Twenty microg/ml G-Rh2 induced the mature and normality of morphology and ultrastructure in SMMC-7721 cells. After treated with 10 microg/ml or 20 microg/ml G-Rh2, the production of AFP was significantly reduced (P< 0.05), and the secretory amount of AFP was reduced from 6.60+/-0.30 to 2.35+/-0.06 (P< 0.01), and the specific activities of gamma-GT and heat-resistant ALP were remarkably declined (P< 0.01); while the secretory amount of albumin and ALP activity were remarkably enhanced (P< 0.01). CONCLUSION: G-Rh2 could induce the SMMC-7721 cell differentiation tending to normal.
PMID: 15301707 [PubMed - in process