n-methoxyindole-3-carbinol and Colonic-Neoplasms

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.

Topics: Cell Cycle; Cell Proliferation; Colonic Neoplasms; Drug Synergism; Drug Therapy, Combination; Humans; Indoles; Tumor Cells, Cultured

Recent results have shown that indole-3-carbinol (I3C) inhibits the cellular growth of human cancer cell lines. In some cruciferous vegetables, another indole, N-methoxyindole-3-carbinol (NI3C), is found beside I3C. Knowledge about the biological effects of NI3C is limited. The aim of the present study was to show the effect of NI3C on cell growth of two human colon cancer cell lines, DLD-1 and HCT-116. For the first time it is shown that NI3C inhibits cellular growth of DLD-1 and HCT-116 and that NI3C is a more potent inhibitor of cell proliferation than I3C. In addition to the inhibition of cellular proliferation, NI3C caused an accumulation of HCT-116 cells in the G2/M phase, in contrast to I3C, which led to an accumulation of the colon cells in G0/G1 phase. Furthermore, NI3C delays the G1-S phase transition of synchronized HCT-116 cells. The indole-mediated cell-cycle arrest may be related to the increased levels of the CDK-inhibitors p21 and p27 (only induced by NI3C). Only an initial increase of cdc2 protein was observed, whereas prolonged treatment with NI3C or I3C downregulates the mRNA and proteins of cyclin-dependent kinases and cyclins. These results indicate that both NI3C and I3C inhibit the proliferation of human colon cells but via different mechanisms.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Genes, cdc; Humans; Indoles; Time Factors