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

Wen Shan Li, Chie Hong Wang, Shengkai Ko, Tzu Ting Chang, Ya Ching Jen, Ching Fa Yao, Shivaji V. More, Shu Chuan Jao

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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 G2-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.

Original languageEnglish
Pages (from-to)1583-1592
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number4
Publication statusPublished - 2012 Feb 23


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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