期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 49, 期 5, 页码 1815-1824出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3703
关键词
mitomycin C; decarbamoyl mitomycin C; p21; p53
类别
资金
- NIH [5SC3GM105460]
- PRISM program at John Jay
- John Jay College of Criminal Justice Start-up Fund
- PRISM fund
- PSC CUNY grant
- US Department of Education
- National Science Foundation
- New York State's Graduate Research and Teaching Initiative
Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (alpha-ICL) has a trans stereochemistry at the guanine-drug linkage whereas the major ICL from DMC (beta-ICL) has the opposite, cis, stereochemistry. In addition, DMC can provoke strong p53-independent cell death. Our hypothesis is that the stereochemistry of the major unique beta-ICL generated by DMC is responsible for this p53-independent cell death signaling. p53 gene is inactively mutated in more than half of human cancers. p21(WAF1/CIP1) known as a major effector of p53 is involved in p53-dependent and-independent control of cell proliferation and death. This study revealed the role of p21(WAF1/CIP1) on MC and DMC triggered cell damage. MCF-7 (p53-proficient) and K562 (p53-deficient) cells were used. Cell cycle distributions were shifted to the G1/S phase in MCF-7 treated with MC and DMC, but were shifted to the S phase in K562. p21(WAF1/CIP1) activation was observed in both cells treated with MC and DMC, and DMC triggered more significant activation. Knocking down p53 in MCF-7 did not attenuate MC and DMC induced p21(WAF1/CIP1) activation. The a-ICL itself was enough to cause p21(WAF1/CIP1) activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据