Open AccessHY ‐1 induces G 2 / M cell cycle arrest in human colon cancer cells through the ATR ‐Chk1‐Cdc25C and Weel pathways
Author(s) -
Zhao Yu,
Wu Zhonghua,
Zhang Yuting,
Zhu Li
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12182
Subject(s) - cyclin dependent kinase 1 , topoisomerase , podophyllotoxin , kinase , cell cycle checkpoint , cancer cell , cyclin b1 , cell cycle , cancer , biology , cancer research , chemistry , microbiology and biotechnology , biochemistry , cell , dna , genetics , stereochemistry
The novel aroylthiourea analogue of podophyllotoxin HY ‐1 (4β‐[benzoyl‐thioureido]‐4‐deoxypodophyllotoxin) was synthesized in our laboratory with the aim of developing multitargeted DNA topoisomerase II inhibitors. The compound showed significant antiproliferative effects on seven cancer cell lines and induced G 2 /M phase arrest in HCT 116 cells. Moreover, HY ‐1 showed a potent inhibitory effect on topoisomerase II ‐mediated kinetoplast DNA decatenation in a dose‐dependent manner. Our results showed that cdc2 phosphorylation and decreased cdc2 kinase acitivity through the ATR ‐Chk1‐Cdc25C and Weel pathways were the central mechanisms for G 2 /M phase arrest in human colon cancer cells.