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

• 作者: Chaojie Wang Fujun Dai Ming Li Qian Li Songqiang Xie Tao Yang Yahong Zhang
• 来源期刊: 细胞凋亡(英文)
• 学科: 医学
• 关键词: Naphthalimide-Polyamine CONJUGATES Apoptosis P53 Mitochondrial TRANSMEMBRANE Potential Oxidative Stress
• 年，卷（期）: 2014,（4）
• 页码范围: 59-69
• 页数: 11页
• 分类号: R73

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.