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Biphasic modulation of cell proliferation by sulforaphane at physiologically relevant exposure times in a human colon cancer cell line

✍ Scribed by Gerlinde Pappa; Helmut Bartsch; Clarissa Gerhäuser


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
697 KB
Volume
51
Category
Article
ISSN
1613-4125

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✦ Synopsis


Abstract

Sulforaphane (SFN), a cancer chemopreventive compound derived from broccoli, is able to induce cell cycle arrest and apoptosis in various tumor cell lines. Here we show that cell growth inhibition by SFN follows a biphasic pattern: Transient exposure of 40‐16 human colon carcinoma cells for up to 6 h resulted in reversible G~2~/M cell cycle arrest and cytostatic growth inhibition even at elevated concentrations, whereas a minimum continuous exposure time of 12 h was necessary for SFN to irreversibly arrest cells in G~2~/M phase and subsequently induce apoptosis. IC~50~ values after 12 h of exposure followed by drug‐free recovery up to 72 h (6.4–8.1 μM) were indistinguishable from those of chronic exposure for 24 to 72 h (5.4–6.6 μM). Low concentrations of SFN caused a transient decrease in glutathione (GSH) levels followed by GSH induction, which may be related to reversible G~2~/M arrest and cytostatic effects. Depletion of GSH does not seem to play a role in SFN‐mediated apoptosis induction. Our data clearly contribute to a better understanding of the kinetics of antiproliferative activity of SFN.