Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition

Iha Park, Kwang Kyun Park, Jung Han Yoon Park, Won Yoon Chung

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Isoliquiritigenin, a natural flavonoid found in licorice, shallots, and bean sprouts, has been demonstrated to inhibit proliferation and to induce apoptosis in a variety of human cancer cells. We attempted to ascertain the underlying mechanism by which isoliquiritigenin induced cell cycle arrest and cytotoxicity in HeLa human cervical cancer cells. Isoliquiritigenin treatment arrested cells in both G2 and M phase. The cells arrested in interphase (G2) showed markers for DNA damage including the formation of γ-H2AX foci and the phosphorylation of ATM and Chk2, whereas the cells arrested in M phase evidenced separate poles and mitotic metaphase-like spindles with partially unaligned chromosomes. The induction of DNA damage and blockade at the metaphase/anaphase transition implied that isoliquiritigenin might function as a topoisomerase II poison, which was further demonstrated via an in vitro topoisomerase II inhibition assay. These results show that isoliquiritigenin inhibits topoiosmerase II activity, and the resultant DNA damage and arrest in mitotic metaphase-like stage contributes to the antiproliferative effects of isoliquiritigenin.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalCancer Letters
Volume277
Issue number2
DOIs
Publication statusPublished - 2009 May 18

Fingerprint

Anaphase
G2 Phase
Metaphase
Cell Division
DNA Damage
Type II DNA Topoisomerase
Shallots
Glycyrrhiza
Poisons
Interphase
Cell Cycle Checkpoints
Flavonoids
Uterine Cervical Neoplasms
isoliquiritigenin
Chromosomes
Phosphorylation
Apoptosis
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{8f03818d5a214c44a69456337980d2fd,
title = "Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition",
abstract = "Isoliquiritigenin, a natural flavonoid found in licorice, shallots, and bean sprouts, has been demonstrated to inhibit proliferation and to induce apoptosis in a variety of human cancer cells. We attempted to ascertain the underlying mechanism by which isoliquiritigenin induced cell cycle arrest and cytotoxicity in HeLa human cervical cancer cells. Isoliquiritigenin treatment arrested cells in both G2 and M phase. The cells arrested in interphase (G2) showed markers for DNA damage including the formation of γ-H2AX foci and the phosphorylation of ATM and Chk2, whereas the cells arrested in M phase evidenced separate poles and mitotic metaphase-like spindles with partially unaligned chromosomes. The induction of DNA damage and blockade at the metaphase/anaphase transition implied that isoliquiritigenin might function as a topoisomerase II poison, which was further demonstrated via an in vitro topoisomerase II inhibition assay. These results show that isoliquiritigenin inhibits topoiosmerase II activity, and the resultant DNA damage and arrest in mitotic metaphase-like stage contributes to the antiproliferative effects of isoliquiritigenin.",
author = "Iha Park and Park, {Kwang Kyun} and Park, {Jung Han Yoon} and Chung, {Won Yoon}",
year = "2009",
month = "5",
day = "18",
doi = "10.1016/j.canlet.2008.12.005",
language = "English",
volume = "277",
pages = "174--181",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition. / Park, Iha; Park, Kwang Kyun; Park, Jung Han Yoon; Chung, Won Yoon.

In: Cancer Letters, Vol. 277, No. 2, 18.05.2009, p. 174-181.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition

AU - Park, Iha

AU - Park, Kwang Kyun

AU - Park, Jung Han Yoon

AU - Chung, Won Yoon

PY - 2009/5/18

Y1 - 2009/5/18

N2 - Isoliquiritigenin, a natural flavonoid found in licorice, shallots, and bean sprouts, has been demonstrated to inhibit proliferation and to induce apoptosis in a variety of human cancer cells. We attempted to ascertain the underlying mechanism by which isoliquiritigenin induced cell cycle arrest and cytotoxicity in HeLa human cervical cancer cells. Isoliquiritigenin treatment arrested cells in both G2 and M phase. The cells arrested in interphase (G2) showed markers for DNA damage including the formation of γ-H2AX foci and the phosphorylation of ATM and Chk2, whereas the cells arrested in M phase evidenced separate poles and mitotic metaphase-like spindles with partially unaligned chromosomes. The induction of DNA damage and blockade at the metaphase/anaphase transition implied that isoliquiritigenin might function as a topoisomerase II poison, which was further demonstrated via an in vitro topoisomerase II inhibition assay. These results show that isoliquiritigenin inhibits topoiosmerase II activity, and the resultant DNA damage and arrest in mitotic metaphase-like stage contributes to the antiproliferative effects of isoliquiritigenin.

AB - Isoliquiritigenin, a natural flavonoid found in licorice, shallots, and bean sprouts, has been demonstrated to inhibit proliferation and to induce apoptosis in a variety of human cancer cells. We attempted to ascertain the underlying mechanism by which isoliquiritigenin induced cell cycle arrest and cytotoxicity in HeLa human cervical cancer cells. Isoliquiritigenin treatment arrested cells in both G2 and M phase. The cells arrested in interphase (G2) showed markers for DNA damage including the formation of γ-H2AX foci and the phosphorylation of ATM and Chk2, whereas the cells arrested in M phase evidenced separate poles and mitotic metaphase-like spindles with partially unaligned chromosomes. The induction of DNA damage and blockade at the metaphase/anaphase transition implied that isoliquiritigenin might function as a topoisomerase II poison, which was further demonstrated via an in vitro topoisomerase II inhibition assay. These results show that isoliquiritigenin inhibits topoiosmerase II activity, and the resultant DNA damage and arrest in mitotic metaphase-like stage contributes to the antiproliferative effects of isoliquiritigenin.

UR - http://www.scopus.com/inward/record.url?scp=62749157517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62749157517&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2008.12.005

DO - 10.1016/j.canlet.2008.12.005

M3 - Article

C2 - 19167809

AN - SCOPUS:62749157517

VL - 277

SP - 174

EP - 181

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -