Stilbene glucosides are naturally occurring phytoalexins, found in a variety of medicinal plants. Among the stilbene derivatives, resveratrol 3-O-D-glucoside (piceid) is found in grapes and wine. We studied the effects of stilbene glucosides isolated from medicinal plants and grapes on tumour growth and lung metastasis in mice bearing highly metastastic Lewis lung carcinoma (LLC) tumours. We also studied the inhibitory effects of stilbene glucosides on differentiation of human umbilical vein endothelial cells (HUVECs) to form a capillary network. Tumour growth in the right hind paw and lung metastasis were inhibited by oral administration of the stilbene glucosides, piceid and 2,3,5,4′-tetrahydroxystilbene-2-O-D-glucoside for 33 consecutive days, in LLC-bearing mice. As the number of CD8+ and NK1.1+ T cells in the spleen was not affected, the inhibitory effects of these stilbene glucosides on tumour growth and lung metastasis could not be explained by natural killer or cytotoxic T lymphocyte activation. Piceid inhibited the DNA synthesis in LLC cells at a concentration of 1000 μm, but not at lower concentrations (10–100 μM). 2,3,5,4′-Tetra-hydroxystilbene-2-O-D-glucoside also inhibited DNA synthesis in LLC cells (IC50 81 μM). In addition, both stilbene glucosides inhibited the formation of capillary-like tube networks (angiogenesis) of HUVECs at concentrations of 100 to 1000 μM. We suggest that the antitumour and antimetastatic activity of the stilbene glucosides, piceid and 2,3,5,4′-tetrahydroxystilbene-2-O-D-glucoside, might be due to the Polygonum multifloriuminhibition of DNA synthesis in LLC cells and angiogenesis of HUVECs.
Lewis lung carcinoma, antitumour activity, piceid, stilbene glucosides
NCBI PubMed ID: 11092574Publication DOI: 10.1211/0022357001777270Journal NLM ID: 0376363Publisher: London: Pharmaceutical Society of Great Britain; West Sussex: Wiley
Correspondence: yokim@m.ehime-u.ac.jp
Institutions: Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Japan
Methods: biological assays, radiolabeling, fluorescence labeling, antitumor activity assay, centrifugation
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