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유전체 항상성 연구단
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A novel chemotherapeutic agent to treat tumors with DNA mismatch repair deficiencies

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Title
A novel chemotherapeutic agent to treat tumors with DNA mismatch repair deficiencies
Author(s)
Zhang Y.; Fox J.T.; Young-Un Park; Elliott G.; Rai G.; Cai M.; Sakamuru S.; Huang R.; Xia M.; Lee K.; Jeon M.H.; Bijoy P. Mathew; Park H.D.; Edelmann W.; Park C.Y.; Sung You Hong; Maloney D.; Kyungjae Myung
Publication Date
2016-07
Journal
CANCER RESEARCH, v.76, no.14, pp.4183 - 4191
Publisher
AMER ASSOC CANCER RESEARCH
Abstract
Impairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutSa-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a MMR-dependent manner. In MutSa-proficient cells, baicalein binds to MutSa to dissociate CHK2 from MutSa leading to S-phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutSa-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutSa-deficient xenograft tumors and inhibits the growth of AOM-DSS-induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency. ©2016 American Association for Cancer Research
URI
https://pr.ibs.re.kr/handle/8788114/2760
ISSN
0008-5472
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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