Estudios científicos

Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells


Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, epsilon-viniferin and its acetylated form, epsilon-viniferin penta-acetate. We also obtained vineatrol, a wine grape shoot extract that associates several polyphenols that may act synergistically, including trans-resveratrol and epsilon-viniferin. We show here that resveratrol triacetate and vineatrol are as efficient as trans-resveratrol in inducing the accumulation of human colon cancer cells in early S phase of the cell cycle. This effect is associated with a nuclear redistribution of cyclin A and the formation of a cyclin A/cyclin-dependent kinase 2 complex whose kinase activity is increased. In contrast, epsilon-viniferin and its acetylated form do not demonstrate any significant activity on these cells when tested alone. Interestingly, resveratrol triacetate and vineatrol dramatically enhance 5-Fluoro-Uracil-mediated inhibition of colon cancer cell proliferation. Thus, acetylated derivatives of resveratrol have retained the cytostatic and cytotoxic activities of the parental molecule and thus deserve to be tested as chemosensitizers in animal models.

Comentarios divulgativos:

Estudios epidemiológicos sugieren que el trans-resveratrol el cual es un componente del vino tinto, puede prevenir el desarrollo de tumores malignos. Este compuesto muestra efectos citotóxicos y citostáticos en el desarrollo de tumores malignos. En este estudio se sintetizan dos derivados del resveratrol: epsilon-viniferin y epsilon-viniferin-penta-acetate así como un extracto del vino: vineatrol. Los resultados muestran que el triacetato de resveratrol y el vineatrol son tan eficientes como el resveratrol induciendo la parada de células cancerígenas de colon en fase S del ciclo celular. Este efecto está asociado con una redistribución de la ciclina A.