title: Photodynamic activities of sulfonamide derivatives of porphycene on nasopharyngeal carcinoma cells.
abstract: 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.
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China. nkmak@hkbu.edu.hk
authors.forename: Nai-Ki
authors.initials: NK
authors.lastname: Mak
authors.forename: Tsz-Wai
authors.initials: TW
authors.lastname: Kok
authors.forename: Ricky Ngok-Shun
authors.initials: RN
authors.lastname: Wong
authors.forename: Sum-Wai
authors.initials: SW
authors.lastname: Lam
authors.forename: Yan-Kin
authors.initials: YK
authors.lastname: Lau
authors.forename: Wing-Nang
authors.initials: WN
authors.lastname: Leung
authors.forename: Nai-Ho
authors.initials: NH
authors.lastname: Cheung
authors.forename: Dolly P
authors.initials: DP
authors.lastname: Huang
authors.forename: Lam-Lung
authors.initials: LL
authors.lastname: Yeung
authors.forename: Chi K
authors.initials: CK
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D015388:Organelles / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013696:Temperature
chemical_list: C482324:PS6 porphyrin; C482325:PS6A porphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins; D013449:Sulfonamides; C051407:porphycene