Photodynamic activities of sulfonamide derivatives of porphycene on nasopharyngeal carcinoma cells.
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.
Mak
Nai-Ki
NK
Department of Biology, Hong Kong Baptist University, Hong Kong, China. nkmak@hkbu.edu.hk
Kok
Tsz-Wai
TW
Wong
Ricky Ngok-Shun
RN
Lam
Sum-Wai
SW
Lau
Yan-Kin
YK
Leung
Wing-Nang
WN
Cheung
Nai-Ho
NH
Huang
Dolly P
DP
Yeung
Lam-Lung
LL
Chang
Chi K
CK
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
C482324:PS6 porphyrin; C482325:PS6A porphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins; D013449:Sulfonamides; C051407:porphycene