[Induction of differentiation by ginsenoside Rh2 in hepatocarcinoma cell SMMC-7721].
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).


CONCLUSIONS
G-Rh2 could induce the SMMC-7721 cell differentiation tending to normal.
Zeng
Xiao-Li
XL
Clinical Laboratory of Anzhen Hospital,Capital University of Medical Sciences, Beijing, 100029, PR China.
Tu
Zhi-Guang
ZG
D000418:Albumins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D005894:Panax / Q000737:chemistry; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000418:Albumins; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D000509:alpha-Fetoproteins; C055305:ginsenoside Rh2; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase