Molecular Targets, Anti-cancer Properties and Potency of Synthetic Indole- 3-carbinol Derivatives

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Author(s): Mojgan Karimabad Noroozi, Mehdi Mahmoodi , Abdolah Jafarzadeh, Ali Darekordi, Mohamad Reza Hajizadeh, Gholamhossein Hassanshahi*.

Journal Name: Mini-Reviews in Medicinal Chemistry

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Abstract:

The indole-3-carbinol (I3C) displays anti-proliferative and anti-cancer activities against human cancer cells. Cellular proliferation is an important event associated with cancer development and continued progression. This manifest is described by altered expression and/or functions of cell cycle related proteins. The constitutive activation of many signal transduction pathways also stimulates cell growth. The immediate stages in tumor development are accompanied by a fibrogenic response and the progression of a hypoxic environment, is in favor of the survival and proliferatory functions of cancer stem cells. The main part for the survival strategy in cancer cells may manifest through altering cell metabolism. The growth and metastasis may be supported by increased generation of appropriate hormones (in hormone dependent cancers), by promoting the development of angiogenesis, with epithelial to mesenchymal transition. This may be facilitated by progression of autophagy phenomenon, as well as by taking cues from neighboring stromal cells. Several signaling pathways in association with various factors specific for cellular viability, including hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor 1 (IGF-1) receptor, Human foreskin fibroblasts (HFF-1), Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling are reported to be inhibited by I3C. These evidences, in combination with bioinformatics data represent very important information for describing signaling pathways in parallel with molecular targets that may provide early diagnostic markers and/or critical targets for designing and development of novel therapeutic regimes alone or combined with drugs, to prevent tumor formation and further progression. Very particularly, I3C and its dimeric product, 3, 3′-diindolylmethane (DIM), have been widely in vestigated for their importance against a number of human cancers both in vitro and in vivo. We aimed the present manuscript, to review an in-depth study of the anticancer properties and the miscellaneous mechanisms underlying the anticarcinogenicity, thereby broadening I3C therapeutic marvel.

Keywords: Indole-3-carbinol, Antitumor, Cell cycle, Apoptosis

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(E-pub Ahead of Print)
DOI: 10.2174/1389557518666181116120145
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