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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 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
Volume55
Issue number4
DOIs
Publication statusPublished - 2012 Feb 23

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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