Resveratrol decreases
cancer risk and improves health of laboratory animals. However, it can also promote
genomic instability. Part of the beneficial activity of
resveratrol may result from the activation of
SIRT1 deacetylase. We examined how
resveratrol influenced the growth of human
cancer cell lines of different origin:
osteosarcoma (U-2 OS) and
lung adenocarcinoma (A549) and how it modulated the expression as well as the localization of key
proteins, involved in DNA repair and cell cycle regulation.
Resveratrol-induced growth arrest was associated with signs of stress-induced senescence. Differential expression of BRCA1,
cyclin B1, pRb and p21 in U-2 OS and A549 cells indicates that
resveratrol can engage various molecular mechanisms to arrest cell cycle progression. In subset of U-2 OS cells, the upregulated BRCA1 formed foci closely associated with WRN and the telomeric
protein (TRF1). Moreover,
resveratrol induced telomeric instability in U-2 OS cells and the activation of DNA damage signaling in both cell lines, manifested as the phosphorylation of
histone H2AX at
serine 139 and of p53 at serines 15 and 37. Our data are consistent with the hypothesis that
resveratrol inhibits cell growth and induces senescence by altering
DNA metabolism.