The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle.
Resveratrol, a natural phytoalexin, has gained much interest on the basis of its potential chemopreventive activity against human cancer. In this work, using the human breast cancer cell lines MCF-7 and MDA-MB-231, we have analyzed a possible mechanism by which resveratrol could interfere with cell cycle control and induce cell death. Our results show that although resveratrol inhibited cell proliferation and viability in both cell lines, apoptosis was induced in a concentration- and cell-specific manner. In MDA-MB-231, resveratrol (up to 200 microM) lowered the expression and kinase activities of positive G1/S and G2/M cell cycle regulators and inhibited ribonucleotide reductase activity in a concentration dependent manner, without a significant effect on the low expression of tumor suppressors p21, p27, and p53. These cells died by a non-apoptotic process in the absence of a significant change in cell cycle distribution. In MCF-7, resveratrol produced a significant and transient (<50 microM) increase in the expression and kinase activities of positive G1/S and G2/M regulators. Simultaneously, p21 expression was markedly induced in presence of high levels of p27 and p53. These opposing effects resulted in cell cycle blockade at the S-phase and apoptosis induction in MCF-7 cells. Thus, the antiproliferative activity of resveratrol could take place through the differential regulation of the cell cycle leading to apoptosis or necrosis. This could be influenced, among other factors, by the concentration of this molecule and by the characteristics of the target cell.
Pozo-Guisado
Eulalia
E
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, Avenida de Elvas s/n, 06071, Badajoz, Spain.
Alvarez-Barrientos
Alberto
A
Mulero-Navarro
Sonia
S
Santiago-Josefat
Belen
B
Fernandez-Salguero
Pedro M
PM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D013267:Stilbenes; D012264:Ribonucleotide Reductases; D000077185:Resveratrol