Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.

There is increasing evidence that diet plays a crucial role in age-related diseases and cancer. Oxidative stress is a conceivable link between diet and diseases, thus food antioxidants, counteracting the damage caused by oxidation, are potential tools for fight age-related diseases and cancer. Resveratrol (RSV), a polyphenolic antioxidant from grapes, has gained enormous attention particularly because of its ability to induce growth arrest and apoptosis in cancer cells, and it has been proposed as both chemopreventive and therapeutic agent for cancer and other diseases. Even though the effects of RSV have been studied in prostate cancer cells and animal models, little is known about its effects on normal cells and tissues. To address this issue, we have investigated the effects of RSV on EPN cells, a human non-transformed prostate cell line, focusing on the relationship between RSV and p66Shc, a redox enzyme whose activities strikingly intersect those of RSV. p66Shc activity is regulated by phosphorylation of serine 36 (Ser36) and has been related to mitochondrial oxidative stress, apoptosis induction, regulation of cell proliferation and migration. Here we show that RSV inhibits adhesion, proliferation and migration of EPN cells, and that these effects are associated to induction of dose- and time-dependent p66Shc-Ser36 phosphorylation and ERK1/2 de-phosphorylation. Moreover, we found that RSV is able to activate also p52Shc, another member of the Shc protein family. These data show that RSV affects non-transformed prostate epithelial cells and suggest that Shc proteins may be key contributors of RSV effects on prostate cells.

Classic Kaposi's sarcoma in southern Sardinia, Italy.

The first examination of classical Kaposi's sarcoma incidence in southern Sardinia (Italy) in 1998-2002 found the highest rate recorded in the island of 2.49 per 100 000 per year (standardised).

From cell death to embryo arrest: mathematical models of human preimplantation embryo development.

Human preimplantation embryos exhibit high levels of apoptotic cells and high rates of developmental arrest during the first week in vitro. The relation between the two is unclear and difficult to determine by conventional experimental approaches, partly because of limited numbers of embryos. We apply a mixture of experiment and mathematical modeling to show that observed levels of cell death can be reconciled with the high levels of embryo arrest seen in the human only if the developmental competence of embryos is already established at the zygote stage, and environmental factors merely modulate this. This suggests that research on improving in vitro fertilization success rates should move from its current concentration on optimizing culture media to focus more on the generation of a healthy zygote and on understanding the mechanisms that cause chromosomal and other abnormalities during early cleavage stages.