Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro

Abstract

A number of previous studies investigated the in vitro effects of resveratrol on malignant human breast epithelial cell replication. The aim of the present study was to evaluate the activity of resveratrol on human metastatic breast cancer cells. The study was performed on the MCF-7 tumor cell line. Cell growth, cell cycle perturbation and apoptosis were evaluated by trypan blue dye exclusion assay, flow cytometric analysis and confocal fluorescence microscopy. TRAP assay and Western blot analysis respectively detected levels of telomerase activity and levels of hTERT in intracellular compartments of MCF-7 cells treated with resveratrol. Resveratrol has a direct inhibitory effect on cell proliferation. The results demonstrate that the drug induces apoptosis in MCF-7 cells, in a time-and concentrationrelated manner. Our results also show that the growth-inhibitory effect of resveratrol on malignant cells is mainly due to its ability to induce S-phase arrest and apoptosis in association with reduced levels of telomerase activity. In particular, TRAP assay and Western blot analysis respectively showed that resveratrol treatment down-regulates the telomerase activity of target cells and the nuclear levels of hTERT, the reverse transcriptase subunit of the telomerase complex. In our experimental model of breast cancer, resveratrol shows direct antiproliferative and pro-apoptotic effects. Studies on telomerase function and intracellular hTERT distribution point out that this agent is endowed with additional suppressive functions on critical tumor biological properties. These results speak in favor of a potential role of resveratrol in chemoprevention/chemotherapy of breast cancer.

Immortalization of epithelial progenitor cells mediated by resveratrol

“…While most resveratrol-mediated effects such as increasing SIRT1 activity, are reported at high micromolar concentrations in transformed cells (Lanzilli et al, 2006) or animal models, a few studies report resveratrol effects at nanomolar and lower concentrations including inhibition of platelet aggregation, neuroprotection through ERK1 and 2 phosphorylation and quinone reductase 2 binding (Miloso et al, 1999;Bhat et al, 2001;Gusman et al, 2001;Bhat and Pezzuto, 2002;Dong, 2003;Signorelli and Ghidoni, 2005). Our data support the pleiotropic effects of resveratrol by showing nanomolar concentrations of resveratrol initiate prosurvival effects by upregulating or reactivating telomerase in progenitor cells (Miloso et al, 1999;Bhat et al, 2001;Gusman et al, 2001;Bhat and Pezzuto, 2002;Dong, 2003;Signorelli and Ghidoni, 2005).…”

“…Similarly, resveratrol facilitated inactivation of p53 in the subpopulation of resveratrol-treated HME50 cells resulting in telomerase activity and cellular immortality (Rambhatla et al, 2001). Studies suggest that resveratrol has different effects based on cell type, conditions and concentration (Signorelli and Ghidoni, 2005;Lanzilli et al, 2006). Higher concentrations are usually more effective on highly proliferative cancer cells (Le Corre et al, 2005;Signorelli and Ghidoni, 2005).…”

Resveratrol: A multitargeted agent for age-associated chronic diseases

“…The compound also decreases the telomerase activity in vitro. 36 There are some recent reports supporting the potential of resveratrol for therapy of osteoporosis. 37,38 It exhibits bone-protective effects equivalent to those exerted by hormone replacement therapy.…”

Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl‐ and Acyl‐ Resveratrol Prodrugs and Resveratrol Sulfate Metabolites

“…This process allows cancer cells to elude the progressive shortening of the telomeres and finally avoid apoptosis. Resveratrol showed an inhibitory effect on MCF-7 tumor cell line mainly due to induce S-phase arrest and apoptosis in association with reduced expression of hTERT (12).…”