1. Academic Validation
  2. Synthesis and evaluation of the cytotoxicities of tetraindoles: observation that the 5-hydroxy tetraindole (SK228) induces G₂ arrest and apoptosis in human breast cancer cells

Synthesis and evaluation of the cytotoxicities of tetraindoles: observation that the 5-hydroxy tetraindole (SK228) induces G₂ arrest and apoptosis in human breast cancer cells

  • J Med Chem. 2012 Feb 23;55(4):1583-92. doi: 10.1021/jm2013425.
Wen-Shan Li 1 Chie-Hong Wang Shengkai Ko Tzu Ting Chang Ya Ching Jen Ching-Fa Yao Shivaji V More Shu-Chuan Jao
Affiliations

Affiliation

  • 1 Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan. wenshan@chem.sinica.edu.tw
Abstract

Current chemical and biological interest in indole-3-carbinol (I3C) and its metabolites has resulted in the discovery of new biologically active indoles. As part of a program aimed at the development of indole analogues, tetraindoles 1-15 were prepared and their antiproliferative effects on human breast Cancer cells were evaluated. The results show that the 5-hydroxy-tetraindole 8 (SK228) has optimum antiproliferative activity against breast adenocarcinoma (MCF 7 and MDA-MB-231) cells and that this activity involves G(2)-phase arrest of the cell cycle with a distinctive increase in the expression of cyclin B1 and phospho-cdc2. Further observations suggest that 5-hydroxy-tetraindole 8 induces Apoptosis through externalization of membrane phosphatidylserine, DNA fragmentation, and activation of Caspase-3. Given the fact that I3C and its metabolites have been shown to improve therapeutic efficacy and to have a broad range of antitumor activities in human Cancer cells, the current findings have important pharmacological relevance as they open a promising route to the development of a potential chemotherapeutic application of tetraindoles as agents for the treatment of breast Cancer.

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