Mechanisms of cell cycle arrest and apoptosis induction by sulforaphane and compinatorial effects of sulforaphane and 3,3'-Diindolylmethane on cancer cell growth inhibition
The chemopreventive isothiocyanate sulforaphane, which is derived from broccoli, was shown to induce a mitotic cell cycle arrest in the human colon cancer cell line 40-16. This arrest was followed by mitochondria-dependent apoptosis. Sulforaphane potently inhibited NF-B activation upstream of its nuclear translocation and decreased the expression of a series of anti-apoptotic, NF-B-dependent genes, which supposedly facilitated apoptosis induction. Transient exposure of 40-16 cells to sulforaphane for up to 6 h resulted in reversible G2/M cell cycle arrest and cytostatic growth inhibition, whereas a minimum continuous exposure time of 12 h was necessary for sulforaphane to irreversibly arrest cells in G2/M and subsequently induce apoptosis. Low concentrations of sulforaphane caused a transient decrease in cytoplasmic glutathione levels followed by glutathione induction after 24 h. However, depletion of glutathione did not seem to play a role for sulforaphane-induced apoptosis. Combination effects of sulforaphane and 3,3’-diindolylmethane were investigated in terms of cell growth inhibition in the 40-16 cell line. Sulforaphane and 3,3’-diindolylmethane inhibited cell proliferation antagonistically at low concentrations, but synergistically at cytotoxic concentrations.