Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10900402 | Cancer Letters | 2005 | 9 Pages |
Abstract
We studied the cytotoxic effects of various DNA replication inhibitors on MMR-deficient and -proficient colon carcinoma cell lines. DNA polymerase (pol) inhibitors including aphidicolin and gemcitabine, and hydroxyurea were more toxic (1.7 to 2.8-fold) to hMLH1-deficient HCT116 than to hMLH1-proficient HCT116+ch3. Similarly, pol inhibitors were more toxic to hMSH2-deficient LoVo than to hMSH2-proficient LoVo+ch2. In contrast, DNA topoisomerase I inhibitors, such as CPT-11, SN-38, and topotecan, were more toxic to MMR-proficient cells. Our results suggest that MMR-deficient colon carcinoma cells are hypersensitive to inhibitors of the pol reaction.
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Authors
Tomonori Takahashi, Zhenghua Min, Iichiro Uchida, Michitsune Arita, Yoh Watanabe, Minoru Koi, Hiromichi Hemmi,