Fausto Berti

Cyclin D3 and p53 mediate sulforaphane-induced cell cycle delay and apoptosis in non-transformed human T lymphocytes.

Abstract. Despite experimental evidence that sulforaphane can exert chemopreventive effects, whether these effects are specific for neoplastic cells is not known. Following our previous demonstration that sulforaphane induces cell cycle arrest and apoptosis in human T lymphoblastoid Jurkat leukemia cells and increases p53 and bax protein expression, we tested sulforaphane on non-transformed phytohemagglutinin-stimulated human lymphocytes. Here, we demonstrate that sulforaphane arrested cell cycle progression in G1 phase, through a decrease in the protein expression of cyclin D3. Moreover, sulforaphane induced apoptosis (and also necrosis), mediated by an increase in the expression of p53. These findings suggest that sulforaphane is a growth modulator for T cells. Our in vitro evidence that sulforaphane is active and even cytotoxic in normal as well as transformed lymphocytes raises important questions regarding its suitability for cancer chemoprevention.

In vitro Antitumor Activity of Cyanidin-3-O-β-Glucopyranoside

Background: Little is currently known regarding the cancer-preventive potential of cyanidin-3-O-β-glucopyranoside (Cy-g) apart from its antioxidant activity. Methods: We tested Cy-g on Jurkat and HL-60 leukemia cell lines and, to help elucidate whether the effects of Cy-g are specific for cancer cells, also on normal T lymphocytes. Results: Cy-g induced apoptosis in all three cell systems, and this indicated that Cy-g was not selective towards leukemia cells. Moreover, Cy-g caused HL-60 differentiation. The induction of apoptosis and cytodifferentiation involved different proteins, thus suggesting that Cy-g-induced apoptosis and cytodifferentiation are two distinct events. Conclusions: Although obtained in vitro, our findings indicate that Cy-g possesses some interesting biological properties that should encourage further investigation as regards its chemotherapeutic potential.

A mutated p53 status did not prevent the induction of apoptosis by sulforaphane, a promising anti-cancer drug

SummaryWe investigated apoptosis induction by sulforaphane on three cell lines characterized by a different p53 status. In particular, we used p53-knock-out fibroblasts from newborn mice transfected with the p53-Ser220 mutation, observed in Li-Fraumeni Syndrome patients, as a model of mutated p53 status. Moreover, immortalized fibroblasts from newborn mice expressing or lacking p53 (p53 +/+ andp53-/-, respectively) have been used to verify whether mutated p53 status could prevent sulforaphane-induced apoptotic events. Sulforaphane was able to induce apoptosis on all three cell lines. Indeed, the caspase-3 assays and poly(ADP-ribose)polymerase (PARP) cleavage data indicated that sulforaphane stimulated caspase-3-like activity and degradation of PARP. However, cells with a wild-type or mutated p53 appeared to be more sensitive to the effects of sulforaphane than cells lacking p53. Taken together, our results suggest that sulforaphane could act by a p53-independent pathway. For this reason, sulforaphane can be viewed as a novel agent useful not only in the treatment of Li-Fraumeni-associated tumors but also drug resistant tumors where p53 dysregulation is a feature.