PuSH - Publication Server of Helmholtz Zentrum München: Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes.

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Fimognari, C.* ; Nüsse, M. ; Berti, F.* ; Iori, R.* ; Cantelli-Forti, G.* ; Hrelia, P.*

Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes.

Ann. NY Acad. Sci. 2010, 393-398 (2003)

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Open Access Green as soon as Postprint is submitted to ZB.

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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 G₂/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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords chemoprevention;isothiocyanates;sulforaphane;apoptosis;cell cycle;cyclins;p53;bcl-2;bax;T lymphocytes;leukemia

ISSN (print) / ISBN 0077-8923

e-ISSN 1749-6632

Journal Annals of the New York Academy of Sciences

Quellenangaben Volume: 2010, Pages: 393-398

Publisher New York Academy of Sciences

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)