title: Ginsenosides 20(S)-protopanaxadiol and Rh2 reduce cell proliferation and increase sub-G1 cells in two cultured intestinal cell lines, Int-407 and Caco-2.
abstract: Ginsenosides derived from 20(S)-protopanaxatriol (PT) and 20(S)-protopanaxadiol (PD) groups had similar characteristic cytotoxic effects on the growth of two intestinal cells lines, Int-407 and Caco-2. Pure Rh2, a ginsenoside structurally related to PD, inhibited intestinal cell growth at greater than twice the concentration of PD, while Rh1, a ginsenoside structurally related to aglycone PT, had no cytotoxic effect. Concentrations causing growth inhibition of 50% of cells (LC50) for the compounds PD, PT, and Rh2 were 23, 26, and 53 microg/mL, respectively, for Int-407 cells. In comparison, the LC50 for PD and PT was determined to be 24 microg/mL, and that for Rh2 was 55 microg/mL in Caco-2 cells. A standardized North American ginseng extract with a known ginsenosides composition did not induce cytotoxicity in either of the intestinal cell lines. Cell cycle analysis showed characteristically different (P = 0.05) effects of ginsenosides PD, Rh2, and PT in both cell lines. Rh2 treatment of Int-407 caused a significantly (P = 0.05) higher production of sub-G1 (apoptotic) cells (35% +/- 1%) compared with untreated cells (14% +/- 0.3%) after 24 h. PD and Rh2 treatments were both significantly (P < 0.05) higher in apoptotic cells than in untreated cells after 48 and 72 h. Similar results were obtained for treatment of Caco-2 cells. Lactate dehydrogenase (LDH) activity in both cell lines was similar for PD and Rh2 and higher (P = 0.05) than for PT treatment at most time periods. These results show a specific structure-function relationship for bioactive ginsenosides in two contrasting intestinal cell types.
authors.affiliation: Food, Nutrition and Health, Faculty of Agricultural Science, University of British Columbia, Vancouver, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Popovich
authors.forename: David D
authors.initials: DD
authors.lastname: Kitts
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D036145:Ginsenosides / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D012502:Sapogenins / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014315:Triterpenes / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014481:United States
chemical_list: D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D012502:Sapogenins; D014315:Triterpenes; C081552:protopanaxatriol; C055305:ginsenoside Rh2; D007770:L-Lactate Dehydrogenase; C062916:protopanaxadiol