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

Abstract

Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.

Resveratrol inhibits ovarian tumor growth in an in vivo mouse model

“…We and others have previously determined that resveratrol induces apoptosis and autophagy and inhibits ovarian carcinoma cell growth in vitro . Stakleff et al determined that orally administered resveratrol did not affect tumor cell growth using a rat model of ovarian carcinoma . Recently, the in vitro and in vivo metabolism of resveratrol has been shown to have profound interindividual differences, which may explain in part the phenomenon behind the “resveratrol paradox,” (low apparent bioavailability with high bioactivity) .…”

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

“…RES’s effects are involved in a variety of cellular pathways against numerous types of cancer models such as melanoma, lung, liver, breast, glioma, prostate, and colorectal (Supplementary Table ). However, the promising in vitro anticancer results were not confirmed in some studies where no overall differences were observed between RES and controls, suggesting that other factors such as dosage, diet, methods and type of tumor could also influence its efficacy [122-127]. RES can inhibit tumor growth from different tissues (prostate, skin, colon, liver, etc.)…”

The pharmacology of resveratrol in animals and humans

“…RSV suppressed the tumor growth of PANC-1 cells orthotopically implanted in nude mice with increased apoptosis/cell cycle arrest proteins including Bim, cleaved caspase-3, and p27, and decreased cell survival/proliferation markers including the expression of PCNA and phosphorylation of ERK, PI3K, Akt, p-FOXO1 (Ser256), and FOXO3a (Ser253) [124]. However, RSV did not show an anti-tumor effect with NuTu-19 ovarian cancers in rats [125], and one study demonstrated that RSV treatment did not affect tumor growth in the CWR22 xenograft model [37].…”