Chu Chu, Xu Jialin, Cheng Dongping, Li Xingnuo, Tong Shengqiang, Yan Jizong, Li Qingyong
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules. 2014 Apr 17;19(4):4941-55. doi: 10.3390/molecules19044941.
Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester (CPT6) is a novel semi-synthetic analog of camptothecin. In a previous report, CPT6 possessed higher cytotoxic activity in vitro towards human breast tumor MCF-7 cells than topotecan. In this study, the antitumor activity of CPT6 on the human breast tumor MCF-7 cell line was analyzed using the MTT method. The underlying mechanism of CPT6 action was investigated by analyzing the cell cycle distribution, apoptotic proportion, changes in mitochondrial membrane potential, and intracellular Ca2+ concentration using flow cytometry. Nuclear and mitochondrial morphologies were also observed by laser scanning confocal and transmission electron microscopy. DNA damage was observed in MCF-7 cells treated with CPT6. Low-dose CPT6 had a significant cytotoxic effect and could inhibit proliferation and induce apoptosis in MCF-7 cells, possibly through cell nucleus fragmentation and DNA damage. CPT6 thus appears to display potent antitumor activity against human breast tumor MCF-7 cells via the induction of apoptosis, and may be a useful alternative drug for breast cancer therapy.
喜树碱-20（s）-O-（2-吡唑基-1）乙酸酯（CPT6）是一种新型的喜树碱半合成类似物。在之前的一份报告中，CPT6在体外对人乳腺肿瘤MCF-7细胞的细胞毒性活性高于拓扑替康。在本研究中，使用MTT法分析了CPT6对人乳腺肿瘤MCF-7细胞系的抗肿瘤活性。通过流式细胞术分析细胞周期分布、凋亡比例、线粒体膜电位变化和细胞内Ca2+浓度，研究了CPT6作用的潜在机制。还通过激光扫描共聚焦显微镜和透射电子显微镜观察了细胞核和线粒体形态。在用CPT6处理的MCF-7细胞中观察到了DNA损伤。低剂量CPT6具有显著的细胞毒性作用，可能通过细胞核碎片化和DNA损伤抑制MCF-7细胞的增殖并诱导其凋亡。因此，CPT6似乎通过诱导凋亡对人乳腺肿瘤MCF-7细胞显示出强大的抗肿瘤活性，可能是乳腺癌治疗的一种有用的替代药物。
