Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate
文献类型：期刊论文
| 作者 | Sun, Xiaoxiao2; Ai, Midan2; Wang, Ying2; Shen, Shensi2; Gu, Yuan2; Jin, Yi1 ; Zhou, Zuyu1; Long, Yaqiu1; Yu, Qiang2
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2013-03-29 |
| 卷号 | 288期号:13页码:8826-8837 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M112.429316 |
| 文献子类 | Article |
| 英文摘要 | Induction of tumor cell apoptosis has been recognized as a valid anticancer strategy. However, therapeutic selectivity between tumor and normal cells has always been a challenge. Here, we report a novel anti-cancer compound methyl 3-(4-nitrophenyl) propiolate (NPP) preferentially induces apoptosis in tumor cells through P450-catalyzed reactive oxygen species (ROS) production. A compound sensitivity study on multiple cell lines shows that tumor cells with high basal ROS levels, low antioxidant capacities, and p53 mutations are especially sensitive to NPP. Knockdown of p53 sensitized non-transformed cells to NPP-induced cell death. Additionally, by comparing NPP with other ROS inducers, we show that the susceptibility of tumor cells to the ROS-induced cell death is influenced by the mode, amount, duration, and perhaps location of ROS production. Our studies not only discovered a unique anticancer drug candidate but also shed new light on the understanding of ROS generation and function and the potential application of a ROS-promoting strategy in cancer treatment. |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; PHENETHYL ISOTHIOCYANATE ; OXIDATIVE STRESS ; MEDIATED MECHANISM ; REDOX REGULATION ; CANCER-CELLS ; IN-VITRO ; GENERATION ; P53 ; CYTOTOXICITY |
| 资助项目 | China Ministry of Science and Technology Key New Drug Creation and Manufacturing Program[2013ZX09102015] ; China Ministry of Science and Technology Research[2013ZX10002010-009] ; China National Natural Science Foundation[31129004] ; China National Natural Science Foundation[91129701] ; China National Natural Science Foundation[91213304] ; National Science and Technology 973 grants[2012CB910704] ; National Science and Technology 973 grants[2013CB910900] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000316862200005 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277686]  |
| 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 | Yu, Qiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Sun, Xiaoxiao,Ai, Midan,Wang, Ying,et al. Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(13):8826-8837. |
| APA | Sun, Xiaoxiao.,Ai, Midan.,Wang, Ying.,Shen, Shensi.,Gu, Yuan.,...&Yu, Qiang.(2013).Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate.JOURNAL OF BIOLOGICAL CHEMISTRY,288(13),8826-8837. |
| MLA | Sun, Xiaoxiao,et al."Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate".JOURNAL OF BIOLOGICAL CHEMISTRY 288.13(2013):8826-8837. |
入库方式： OAI收割
来源：上海药物研究所
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