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Pharmacological exploitation of indole-3-carbinol to develop potent antitumor agents.

The antitumor activity of indole-3-carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells, especially those mediated by EGFR/Src, Akt, NF-kB, endoplasmic reticulum stress, and nuclear receptors. This broad spectrum of antitumor activities in conjunction with its metabolic instability constitutes the rationale for the structural modifications of indole-3-carbinol and its metabolite diindoylmethane to develop novel classes of antitumor agents with improved potency and distinct mechanisms. Thus, this minireview focuses on the chemical biology of the lead optimization of these indole derivatives.