title: Selective induction of tumor cell apoptosis by a novel P450-mediated reactive oxygen species (ROS) inducer methyl 3-(4-nitrophenyl) propiolate.
abstract: 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.
authors: Departments of Pharmacology, Chinese Academy of Sciences, 555 Zhchongzhi Road, Shanghai, China 201203.
authors: Xiaoxiao
authors: X
authors: Sun
authors: Midan
authors: M
authors: Ai
authors: Ying
authors: Y
authors: Wang
authors: Shensi
authors: S
authors: Shen
authors: Yuan
authors: Y
authors: Gu
authors: Yi
authors: Y
authors: Jin
authors: Zuyu
authors: Z
authors: Zhou
authors: Yaqiu
authors: Y
authors: Long
authors: Qiang
authors: Q
authors: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D056945:Hep G2 Cells; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000737:chemistry* / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010666:Phenylpropionates; D011422:Propionates; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C581315:methyl 3-(4-nitrophenyl)propiolate; D045304:Cytochromes c; D003577:Cytochrome P-450 Enzyme System; D053613:Janus Kinase 1
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