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MINS, a Novel Naphthalimide-Polyamine Conjugate, Induced Apoptosis Depending on p53 Status in Human Colon Cancer Cells

MINS, a Novel Naphthalimide-Polyamine Conjugate, Induced Apoptosis Depending on p53 Status in Human Colon Cancer Cells
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摘要 Natural polyamine is an ideal antitumor drug carrier because of the great requirement difference between cancer cells and normal cells. Previous data demonstrated that many cytotoxic drugs conjugated with natural or synthetic polyamines have potent antitumor effects. Up to now, the antitumor mechanism of conjugates of naphthalimides with polyamine remains poorly understood in human colon cancer cells. The aim of this study is to evaluate the effect of MINS (a novel naph-thalimide-polyamine conjugate) and mechanism of MINS in human colon cancer cells. Mitochondrial toxicity, which was generated by ROS from mitochondria electron transport chain, might be a major factor in MINS-inducted apoptosis. Our data also demonstrated that MINS-mediated cell apoptosis depend on p53 status, for MINS induced Caco-2 cells (p53 null) only necrosis but not apoptosis. Furthermore, the apoptotic effect of MINS is stronger than that of Amonafide, the parent drug of MINS. Our data suggested that the MINS-mediated cell apoptosis depend on p53 in human colon cancer cells. Natural polyamine is an ideal antitumor drug carrier because of the great requirement difference between cancer cells and normal cells. Previous data demonstrated that many cytotoxic drugs conjugated with natural or synthetic polyamines have potent antitumor effects. Up to now, the antitumor mechanism of conjugates of naphthalimides with polyamine remains poorly understood in human colon cancer cells. The aim of this study is to evaluate the effect of MINS (a novel naph-thalimide-polyamine conjugate) and mechanism of MINS in human colon cancer cells. Mitochondrial toxicity, which was generated by ROS from mitochondria electron transport chain, might be a major factor in MINS-inducted apoptosis. Our data also demonstrated that MINS-mediated cell apoptosis depend on p53 status, for MINS induced Caco-2 cells (p53 null) only necrosis but not apoptosis. Furthermore, the apoptotic effect of MINS is stronger than that of Amonafide, the parent drug of MINS. Our data suggested that the MINS-mediated cell apoptosis depend on p53 in human colon cancer cells.
作者 Ming Li Tao Yang Fujun Dai Qian Li Yahong Zhang Songqiang Xie Chaojie Wang
机构地区 Institute of Chemical Biology The Key Laboratory of Natural Medicine and Immuno-Engineering
出处 《Open Journal of Apoptosis》 2014年第4期59-69,共11页 细胞凋亡（英文）
关键词 Naphthalimide-Polyamine CONJUGATES Apoptosis P53 Mitochondrial TRANSMEMBRANE Potential Oxidative Stress Naphthalimide-Polyamine Conjugates Apoptosis p53 Mitochondrial Transmembrane Potential Oxidative Stress
分类号 R73 [医药卫生—肿瘤]
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共引文献18

Open Journal of Apoptosis
2014年 第4期

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