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In this paper, we present evidence that ginsenoside-Rs4 (G-Rs4; an acetylated analogue of ginsenoside-Rg5), a new ginseng saponin isolated from Panax ginseng C. A. Meyer, elevates protein levels of p53 and p21WAF1, which are associated with the induction of apoptosis in SK-HEP-1 cells. Flow cytometric analyses showed that G-Rs4 initially arrested the cell cycle at the G1/S boundary, but consequently induced apoptosis as evidenced by generating an apoptotic peak. The induction of apoptosis was confirmed by the results of DNA fragmentation assays and alterations in cell morphology after treatment of the cells with G-Rs4. Immunoblot assays showed that G-Rs4 significantly elevated protein levels of p53 and p21WAF1, concurrently with the downregulation of both cyclins E- and A-dependent kinase activities and induction of apoptosis. We suggest that G-Rs4 induces apoptosis, the effect of which is closely related to the downregulation of both cyclins E- and A-dependent kinase activity as a consequence of selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells.

apoptosis, p53, ginsenoside-Rs4, p21WAF1, CDK2

NCBI PubMed ID: 10448308
Publication DOI: 10.1016/s0959-8049(98)00415-8
Journal NLM ID: 9005373
Publisher: Oxford: Elsevier Science
Correspondence: Lee SK
Institutions: College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
Methods: 13C NMR, 1H NMR, IR, FAB-MS, DNA techniques, radiolabeling, immunoblotting, statistical analysis, flow cytometry, antitumor activity assay, MTT, apoptosis assay, phase contrast microscopy, histone H1 kinase assays

Triterpenoid and steroidal glycosides, referred to collectively as saponins, are bioactive compounds present naturally in many plants. They have considerable potential as pharmaceutical and/or nutraceutical agents in natural or synthetic form. Saponins, from a variety of sources, have been shown to have hypocholesterolemic, anticoagulant, anticarcinogenic, hepatoprotective, hypoglycemic, immunomodulatory, neuroprotective, anti-inflammatory and anti-oxidant activity. This paper reviews saponin research of the last decade, focussing on developments in understanding their mechanism of action and structure-activity relationships. Virtually all of this work has used animal and in vitro models. To date there are very few human data.

immunomodulation, hypoglycemic activity, antiinflammatory activity, anti-oxidant activity, Hepatoprotection, steroidal glycosides, saponins, neuroprotection, triterpenoid glycosides, hypocholesterolemic activity, anti-coagulation, anticarcinogen

NCBI PubMed ID: 11201296
Publication DOI: 10.1515/dmdi.2000.17.1-4.211
Journal NLM ID: 8904736
Publisher: Berlin: De Gruyter
Correspondence: v.rao@utoronto.ca
Institutions: Department of Nutritional Sciences, University of Toronto, Toronto, Canada