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

Research output: Contribution to journalArticle

17 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

Fingerprint

Observation
Apoptosis
Breast Neoplasms
Cyclin B1
Indoles
G2 Phase
Phosphatidylserines
DNA Fragmentation
Cell Cycle Checkpoints
Human Activities
Caspase 3
Adenocarcinoma
Breast
1,4-bis(di(5-hydroxy-1H-indol-3-yl)methyl)benzene
Pharmacology
Membranes
Neoplasms
indole-3-carbinol
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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

In: Journal of Medicinal Chemistry, Vol. 55, No. 4, 23.02.2012, p. 1583-1592.

Research output: Contribution to journalArticle

Li, Wen Shan ; Wang, Chie Hong ; Ko, Shengkai ; Chang, Tzu Ting ; Jen, Ya Ching ; Yao, Ching Fa ; More, Shivaji V. ; Jao, Shu Chuan. / 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. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 4. pp. 1583-1592.
@article{6a88ab7b1d124b15ab329f8467ca71f1,
title = "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",
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.",
author = "Li, {Wen Shan} and Wang, {Chie Hong} and Shengkai Ko and Chang, {Tzu Ting} and Jen, {Ya Ching} and Yao, {Ching Fa} and More, {Shivaji V.} and Jao, {Shu Chuan}",
year = "2012",
month = "2",
day = "23",
doi = "10.1021/jm2013425",
language = "English",
volume = "55",
pages = "1583--1592",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Synthesis and evaluation of the cytotoxicities of tetraindoles

T2 - Observation that the 5-hydroxy tetraindole (SK228) induces G2 arrest and apoptosis in human breast cancer cells

AU - Li, Wen Shan

AU - Wang, Chie Hong

AU - Ko, Shengkai

AU - Chang, Tzu Ting

AU - Jen, Ya Ching

AU - Yao, Ching Fa

AU - More, Shivaji V.

AU - Jao, Shu Chuan

PY - 2012/2/23

Y1 - 2012/2/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863128976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863128976&partnerID=8YFLogxK

U2 - 10.1021/jm2013425

DO - 10.1021/jm2013425

M3 - Article

C2 - 22277074

AN - SCOPUS:84863128976

VL - 55

SP - 1583

EP - 1592

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 4

ER -