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ToxSci Advance Access published online on October 13, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfi008
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received August 2, 2004
Accepted September 28, 2004

In Vitro Toxicology

Characterization of the N-Methoxyindole-3-Carbinol (NI3C)-Induced Cell Cycle Arrest in Human Colon Cancer Cell Lines

Antje S. Neave 1, Sussi M. Sarup 1, Michel Seidelin 1, Fritz Duus 1, and Ole Vang 1*

1 Department of Life Sciences and Chemistry, Roskilde University, Roskilde, Denmark

* To whom correspondence should be addressed. E-mail: ov{at}ruc.dk.


  Abstract

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 compared to I3C. Concurrent to the inhibition of cellular proliferation, NI3C caused an accumulation of HCT-116 cells in the G2/M phase, in contrast to I3C, which lead to an accumulation of the colon cells in G0/G1 phase. Furthermore, NI3C delays the G1-S phase transition of synchronised 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 down-regulates the mRNA and proteins of cdks and cyclins. These results indicate that both NI3C and I3C inhibit the proliferation of human colon cells but via different mechanisms.

Keywords: N-methoxyindole-3-carbinol; indole-3-carbinol; colon cells; cell cycle; cell proliferation; carcinogenesis.
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