Oligomannurarate sulfate sensitizes cancer cells to doxorubicin by inhibiting atypical activation of NF-?B via targeting of Mre11
文献类型：期刊论文
| 作者 | Zhang, Jing; Xin, Xianliang; Chen, Qin; Xie, Zuoquan ; Gui, Min; Chen, Yi; Lin, Liping; Feng, Jianming; Li, Qiuning; Ding, Jian
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| 刊名 | INTERNATIONAL JOURNAL OF CANCER
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| 出版日期 | 2012-01-15 |
| 卷号 | 130期号:2页码:467-477 |
| 关键词 | oligosaccharide sulfate NF-?B inhibitor doxorubicin Mre11 DNA double-strand breaks |
| ISSN号 | 0020-7136 |
| DOI | 10.1002/ijc.26021 |
| 文献子类 | Article |
| 英文摘要 | Aberrant regulation of nuclear factor kappa B (NF-?B) transcription factor is involved in cancer development, progression and resistance to chemotherapy. JG3, a marine-derived oligomannurarate sulfate, was reported as a heparanase and NF-?B inhibitor to significantly block tumor growth and metastasis in various animal models. However, the detailed functional mechanism remains unclear. Here, we report that JG3 inhibits NF-?B activation by specifically antagonizing the doxorubicin-triggered Ataxia-telangiectasia-mutated kinase (ATM) and the sequential MEK/ERK/p90Rsk/IKK signaling pathway but does not interfere with TNF-a-mediated NF-?B activation. This selective inactivation of the specific NF-?B cascade is attributed to the binding capacity of JG3 for Mre11, a major sensor of DNA double-strand breaks (DSB). Based on this selective mechanism, JG3 showed synergistic effect with doxorubicin in a panel of tumor cells and did not affect immune system function as shown in the in vivo delayed-type hypersensitivity (DTH) and hemolysis assays. All these highlight the clinical potential of JG3 as a favorable sensitizer in cancer therapy. In addition, identification of Mre11 as a potential target in the development of NF-?B inhibitors provides a platform for the further development of effective anticancer agents. |
| WOS关键词 | FACTOR-KAPPA-B ; DOUBLE-STRAND BREAKS ; MEDIATED DOWN-REGULATION ; ENHANCED CHEMOSENSITIVITY ; SIGNALING PATHWAYS ; GENOTOXIC STRESS ; P65 SUBUNIT ; DNA-DAMAGE ; ATM ; PROGRESSION |
| 资助项目 | Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; National Basic Research Program Grant of China[2003CB716400] ; Natural Science Foundation of China for Innovation Research Group[30721005] ; Chinese Academy of Sciences[KSCX2-YWR-25] ; Key New Drug Creation and Manufacturing Program[2009ZX09103-073] ; 863 Hi-Tech Program of China[2006AA020602] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000298254400023 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278219]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Geng, Meiyu |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Jing,Xin, Xianliang,Chen, Qin,et al. Oligomannurarate sulfate sensitizes cancer cells to doxorubicin by inhibiting atypical activation of NF-?B via targeting of Mre11[J]. INTERNATIONAL JOURNAL OF CANCER,2012,130(2):467-477. |
| APA | Zhang, Jing.,Xin, Xianliang.,Chen, Qin.,Xie, Zuoquan.,Gui, Min.,...&Geng, Meiyu.(2012).Oligomannurarate sulfate sensitizes cancer cells to doxorubicin by inhibiting atypical activation of NF-?B via targeting of Mre11.INTERNATIONAL JOURNAL OF CANCER,130(2),467-477. |
| MLA | Zhang, Jing,et al."Oligomannurarate sulfate sensitizes cancer cells to doxorubicin by inhibiting atypical activation of NF-?B via targeting of Mre11".INTERNATIONAL JOURNAL OF CANCER 130.2(2012):467-477. |
入库方式： OAI收割
来源：上海药物研究所
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