Mak Nai-Ki, Kok Tsz-Wai, Wong Ricky Ngok-Shun, Lam Sum-Wai, Lau Yan-Kin, Leung Wing-Nang, Cheung Nai-Ho, Huang Dolly P, Yeung Lam-Lung, Chang Chi K
Department of Biology, Hong Kong Baptist University, Hong Kong, China.
J Biomed Sci. 2003 Jul-Aug;10(4):418-29. doi: 10.1007/BF02256433.
Two sulfonamide derivatives of porphycene, namely PS6 and PS6A, were synthesized, and their photodynamic efficacies on the nasopharyngeal carcinoma (NPC) cell line NPC/CNE-2 were evaluated. By comparing the 50% lethal concentrations (LC(50)) of these photosensitizers, we found that PS6A with a cationic ammonium group on the side chain exhibited potent photocytotoxicity on the NPC cell line. At a light dose of 1 J/cm(2), the LC(50) values of PS6 and PS6A for NPC cells were 11.6 and 1.92 microM, respectively. CNE-2 was found to rapidly take up PS6A in the first hour of incubation, and the uptake kinetics steadily increased to a plateau level after 18 h of incubation. The uptake of PS6A was temperature dependent. Over 99% of CNE-2 cells were sensitized by PS6A 24 h after drug treatment. Collapse of the mitochondrial membrane potential was also observed in PS6A photodynamic therapy (PDT)-treated CNE-2 cells 1.5 h after PDT. Confocal microscopy revealed that PS6A was predominantly localized in the mitochondria, lysosomes and Golgi bodies of NPC cells. Significant genotoxicity was not observed in CNE-2 cells. In functional studies, the in vitro formation of a capillary-like network of human umbilical vein endothelial cells in Matrigel was greatly inhibited by PS6A PDT in a dose-dependent manner. In conclusion, PS6A mediates both in vitro antitumor and antiangiogenic activities. PS6A might be a candidate for photodynamic treatment of NPCs.
合成了二萘嵌苯的两种磺胺衍生物，即PS6和PS6A，并评估了它们对鼻咽癌（NPC）细胞系NPC/CNE-2的光动力疗效。通过比较这些光敏剂的50%致死浓度（LC(50)），我们发现侧链带有阳离子铵基团的PS6A对NPC细胞系表现出强大的光细胞毒性。在光剂量为1 J/cm(2)时，PS6和PS6A对NPC细胞的LC(50)值分别为11.6和1.92 microM。发现CNE-2在孵育的第一个小时内迅速摄取PS6A，并在孵育18小时后摄取动力学稳定增加至平台期水平。PS6A的摄取是温度依赖性的。药物处理24小时后，超过99%的CNE-2细胞被PS6A致敏。在PS6A光动力疗法（PDT）处理的CNE-2细胞中，PDT 1.5小时后也观察到线粒体膜电位的崩溃。共聚焦显微镜显示，PS6A主要定位于NPC细胞的线粒体、溶酶体和高尔基体中。在CNE-2细胞中未观察到明显的遗传毒性。在功能研究中，PS6A PDT以剂量依赖性方式极大地抑制了基质胶中人类脐静脉内皮细胞体外毛细血管样网络的形成。总之，PS6A介导体外抗肿瘤和抗血管生成活性。PS6A可能是NPC光动力治疗的候选药物。
