Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy
Subhash B. Padhye,
Fazlul H. Sarkar.
Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its
dimeric product, 3,3'-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling
pathways, including PI3K/Akt/mTOR signaling pathway. These natural compounds are also effective modulators of downstream
transcription factor NF-κB signaling which might help explain their ability to inhibit invasion and angiogenesis, and the reversal of
epithelial-to-mesenchymal transition (EMT) phenotype and drug resistance. Signaling through PI3K/Akt/mTOR and NF-κB pathway is
increasingly being realized to play important role in EMT through the regulation of novel miRNAs which further validates the
importance of this signaling network and its regulations by indole compounds. Here we will review the available literature on the
modulation of PI3K/Akt/mTOR/NF-κB signaling by both parental I3C and DIM, as well as their analogs/derivatives, in an attempt to
catalog their anticancer activity.
Keywords: Indole compounds, PI3K, cancer therapy, NF-κB, Glucosinolates.
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