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

生物 Wnt信号通路 癌细胞 癌症研究 癌症干细胞 信号转导 血管生成 癌症 PI3K/AKT/mTOR通路 蛋白激酶B 间质细胞 上皮-间质转换 细胞生物学 转移 干细胞 遗传学
作者
Mojgan Noroozi Karimabad,Mehdi Mahmoodi,Abdollah Jafarzadeh,Ali Darekordi,Mohamad Reza Hajizadeh,Gholamhossein Hassanshahi
出处
期刊:Mini-reviews in Medicinal Chemistry [Bentham Science Publishers]
卷期号:19 (7): 540-554 被引量:22
标识
DOI:10.2174/1389557518666181116120145
摘要

The indole-3-carbinol (I3C) displays anti-cancer/proliferative activities against human cancer cells. Cellular proliferation is an event associated with the progress and its continuation. This manifest is described by variation in expression and/or functions of genes that are related with cell cycle relevant proteins. The constitutive activation of several signal transduction pathways stimulates cells proliferation as well. The immediate stages in cancer development are accompanied by a fibrogenic response and the progression of the hypoxic environment is in favor of survival and proliferatory functions of cancer stem cells. A main part for prevention of in cancer cells death may manifest through altering cell metabolism. Cellular proliferation and metastasis are reported to be supported with increased generation of responsible hormones (in hormone dependent malignancies), and further promotion the angiogenesis, with epithelial to mesenchymal transition. This may be facilitated by progression of autophagy phenomenon, as well as via taking cues from neighboring stromal cells. Several signaling pathways in association with various factors specific for cellular viability, including hypoxia inducible factor 1, NF-κB, insulin-like growth factor 1 (IGF-1) receptor, Human foreskin fibroblasts (HFF-1), phosphoinositide 3 kinase/Akt, Wnt, cell cycle related protein, with androgen and estrogen receptor signaling are reported to be inhibited by I3C. These evidences, in association with bioinformatics data represent very important information for describing signaling pathways in parallel with molecular targets that may serve as markers for early diagnosis and/or critical targets for designing and development of novel therapeutic regimes alone or combined with drugs, to prevent tumor formation and further progression. In particular, I3C and DIM have been extensively investigated for their importance against numbers human cancers both in vitro and in vivo. We aimed the present manuscript, current study, to review anticancer properties and the miscellaneous mechanisms underlying the antitumorigenicity in an in-depth study for broadening the I3C treating marvel.

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