Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro.
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 concentration-related 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.
Lanzilli
Giulia
G
Institute of Neurobiology and Molecular Medicine, CNR, Area Ricerca Roma 'Tor Vergata', I-00133 Rome, Italy. giulia.lanzilli@artov.inmm.cnr.it
Fuggetta
Maria Pia
MP
Tricarico
Maria
M
Cottarelli
Andrea
A
Serafino
Annalucia
A
Falchetti
Roberto
R
Ravagnan
Giampietro
G
Turriziani
Mario
M
Adamo
Riccardo
R
Franzese
Ornella
O
Bonmassar
Enzo
E
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D019098:Telomerase; D000077185:Resveratrol