Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes.
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.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, 40126 Bologna, Italy. fimognari@biocfarm.unibo.it
Nüsse
Michael
M
Berti
Fausto
F
Iori
Renato
R
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D006801:Humans; D017879:Isothiocyanates; D019169:Jurkat Cells; D013454:Sulfoxides; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane