Resveratrol Is Rapidly Metabolized in Athymic (Nu/Nu) Mice and Does Not Inhibit Human Melanoma Xenograft Tumor Growth

Abstract

Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 micromol/L or 263 micromol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10-100 mg resveratrol were implanted into the mice, next to newly palpated tumors, and tumor growth determined. We also determined the effect of a major resveratrol metabolite, piceatannol, on experimental lung metastasis. Resveratrol, at any concentration tested, did not have a statistically significant effect on tumor growth. The higher levels of resveratrol tested (0.006% in food or 100 mg in slow-release pellets) tended to stimulate tumor growth (P = 0.08-0.09). Resveratrol and its major metabolites, resveratrol glucuronide and piceatannol, were found in serum, liver, skin, and tumor tissue. Piceatannol did not affect the in vitro growth of a murine melanoma cell line, but significantly stimulated the number of lung metastases when these melanoma cells were directly injected into the tail vein of the mouse. These results suggest that resveratrol is not likely to be useful in the treatment of melanoma and that the effects of phytochemicals on cell cultures may not translate to the whole animal system.

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

“…administration for 23 days starting at the same time of tumor cell inoculation. Similarly, dietary resveratrol did not affect the growth of xenografted A375 human melanoma cells in mice (Niles et al, 2006) in spite of inhibiting the growth of the same malignant cells in vitro (Niles et al, 2003). The aforementioned studies indicate that the in vivo antitumor effects of resveratrol could be dependent on the experimental models used.…”

Synthesis of glycosides of resveratrol, pterostilbene, and piceatannol, and their anti-oxidant, anti-allergic, and neuroprotective activities

“…It exhibits immunosuppressive, anti-oxidative, and antitumorigenic activities. [8][9][10] Despite the bio-and physiological activities of these stilbene compounds, their use as medicines has been limited, due to their insolubility in water and poor absorption after oral administration.…”

Synthesis of Glycosides of Resveratrol, Pterostilbene, and Piceatannol by Glucosyltransferase from Phytolacca americana Expressed in Bacillus subtilis and their Chemopreventive Activity Against Cancer, Allergic, and Alzheimer’s Diseases

“…Among the glycosides tested, resveratrol 3-β-glucoside (2) decreased KB cell invasion. Invasion was drastically decreased in cells treated with resveratrol (1), pterostilbene (4), and piceatannol (6). Other glycosides 3, 5, and 7 showed little inhibitory effects.…”

“…As a result, pterostilbene (4) and pterostilbene 4′-β-glucoside (5) showed high PDE inhibitory activity. On the other hand, resveratrol 3-β-glucoside (2), resveratrol 4′-β-glucoside (3), piceatannol (6), and piceatannol 4′-β-glucoside (7) had low inhibitory activity against PDE.…”

“…It exhibits immunosuppressive, anti-oxidation activity, and antitumorigenic activities. 3,4 The water-insolubility of stilbenes such as resveratrol, pterostilbene, and piceatannol limits their further pharmacological exploitation. Glycosylation allows water-insoluble and unstable organic compounds to be converted into the corresponding water-soluble and stable compounds.…”