Mechanisms of cell cycle arrest and apoptosis induction by sulforaphane and combinatorial 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.