Open AccessInduction of mitotic cell death in cancer cells by small interference RNA suppressing the expression of RecQL1 helicase
Author(s) -
Futami Kazunobu,
Kumagai Emi,
Makino Hiroshi,
Goto Hideyuki,
Takagi Motoki,
Shimamoto Akira,
Furuichi Yasuhiro
Publication year - 2008
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.1349-7006.2007.00647.x
Subject(s) - mitotic catastrophe , mitosis , biology , microbiology and biotechnology , recq helicase , dna damage , helicase , cell cycle , cancer cell , dna repair , cell growth , gene silencing , g2 m dna damage checkpoint , programmed cell death , rna helicase a , cell , cancer research , cell cycle checkpoint , cancer , genome instability , dna , genetics , rna , gene , apoptosis
RecQL1 DNA helicase of the human RecQ helicase family participates in DNA repair and recombination pathways during cell‐cycle replication. When we examined the effect of RecQL1 suppression on cell growth, we found that RecQL1 silencing by small interference RNA efficiently prevented proliferation of a wide range of cancer cells by inducing mitotic catastrophe and mitotic cell death. In contrast, such mitotic cell death was not seen in the growing normal fibroblasts used as controls, even if RecQL1 expression was fully downregulated. Our results support the hypothesis that endogenous DNA damage that occurs during DNA replication and remains unrepaired in cancer cells due to RecQL1 silencing induces cancer cell‐specific mitotic catastrophe through a less‐strict checkpoint in cancer cells than in normal cells. We speculate that normal cells are exempt from such mitotic cell death, despite slow growth, because cell‐cycle progression is controlled strictly by a strong checkpoint system that detects DNA damage and arrests progression of the cell cycle until DNA damage is repaired completely. These results suggest that RecQL1 helicase is an excellent molecular target for cancer chemotherapy. ( Cancer Sci 2008; 99: 71–80)