Isothiocyanates exert chemopreventive effects against chemically induced
tumors in animals, modulating
enzymes required for
carcinogens' activation/detoxification and/or the induction of cell-cycle arrest and apoptosis in tumor cell lines. To investigate the chemopreventive potential of
isothiocyanates, we studied proliferation, apoptosis induction and p53, bcl-2 and
bax protein expression in Jurkat T-
leukemia cells by the
isothiocyanate sulforaphane.
Sulforaphane caused G(2)/M-phase delay and increase of apoptotic cell fraction in a time- and dose-dependent manner.
Necrosis was observed after prolonged exposure to elevated
sulforaphane doses. Moreover, it markedly increased p53 and
bax protein expression, and slightly affected bcl-2 expression. Since selective targeting and low toxicity for normal host tissues are fundamental requisites for proposed chemopreventive agents such as
sulforaphane, we tested
sulforaphane on non-transformed
phytohemagglutinin-stimulated human T-lymphocytes. We demonstrated that
sulforaphane arrested cell-cycle progression in G1 phase by a significant down-modulation of
cyclin D3. Moreover,
sulforaphane induced apoptosis (and also
necrosis), mediated by an increase in the expression of p53, whereas it exerted little effect on bcl-2 and bax levels. These findings indicate that
sulforaphane can exert protective effects inhibiting leukemic cell growth. Moreover,
sulforaphane is active not only in transformed lymphocytes but also in their normal counterpart. Although in vitro studies do not necessarily predict in vivo outcomes, our findings raise important questions regarding the suitability of
sulforaphane for
cancer chemoprevention.