Open AccessAnalysis of inhibition of topoisomerase IIα and cancer cell proliferation by ingenolEZ
Author(s) -
Yoshida Chisato,
Hishiyama Kazsuyoshi,
Miyazaki Khosuke,
Watanabe Manami,
Kanbe Masahiro,
Yamada Yuta,
Matsuzaki Keiithi,
Miyashita Kiichi,
Kitanaka Susumu,
Miyata Shohei
Publication year - 2010
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/j.1349-7006.2009.01408.x
Subject(s) - topoisomerase , cell cycle checkpoint , cell cycle , cell growth , dna damage , g2 m dna damage checkpoint , inhibitory postsynaptic potential , microbiology and biotechnology , growth inhibition , mitosis , chemistry , cell culture , biology , cell , cancer research , biochemistry , dna , genetics , endocrinology
We previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase inhibitory activity and/or inhibitory activity of cell proliferation. The inhibitory effects of 20‐ O‐ (2′ E ,4′ Z ‐decadienoyl) ingenol and 3‐ O ‐(2′ E ,4′ Z‐ decadienoyl)‐ingenol among these compounds on topoisomerase II activity and on the cell proliferative activity and arrest phase of the cell cycle were studied using a mouse breast cancer (MMT) cell line. Although 20‐ O ‐ingenolEZ exerted inhibitory effects on both topoisomerase II activity and cell proliferative activity, 3‐ O ‐ingenolEZ exerted inhibitory activity on neither. The 20‐ O ‐ingenolEZ‐induced cell arrest of MMT‐cell proliferation led to a cell cycle arrest in the G2/M phase. Topoisomerase II inhibition can be divided into the poison and catalytic inhibitor types. A checkpoint mechanism is activated when cells are treated with these topoisomerase II inhibitors. Poison‐type inhibition occurs via induction of the DNA damage checkpoint and the catalytic‐type inhibition occurs via induction of the DNA‐decatenation checkpoint, suggestive of distinct checkpoint reactions. 20‐ O‐ ingenolEZ inhibited topoisomerase IIα activity through inhibition of ATPase, and induced DNA‐decatenation checkpoint without signaling for phosphorylation of H2AX. ( Cancer Sci 2010; 101: 374–378)