Biphasic modulation of cell proliferation by sulforaphane at physiologically relevant exposure times in a human colon cancer cell line.
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 microM) were indistinguishable from those of chronic exposure for 24 to 72 h (5.4-6.6 microM). 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.
Pappa
Gerlinde
G
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bartsch
Helmut
H
Gerhäuser
Clarissa
C
D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D016195:G2 Phase / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D006801:Humans; D017879:Isothiocyanates; D007700:Kinetics; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage*; D013997:Time Factors
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D005978:Glutathione