Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol.
Consumption of cruciferous vegetables and cancer prevention seem to be positively associated. We present an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle. However, 200 microM 4MeOI3C caused a very high level of cell death and an accumulation of living cells in the G(0)/G(1) phase, indicating a concentration-dependent mode of action. We conclude that 4MeOI3C might play a role in the cancer preventive effect of cruciferous vegetables.
Kronbak
Remy
R
Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark.
Duus
Fritz
F
Vang
Ole
O
D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007211:Indoles; C410766:N-methoxyindole-3-carbinol; C016517:indole-3-carbinol