title: Efficacy of hypocrellin pharmacokinetics in phototherapy.
abstract: Hypocrellins A and B are pigments which are isolated from the parasitic fungi Hypocrella bambuase sacc and Shiraia bambusicola P. Heen found in the People's Republic of China and other parts of Asia including Sri Lanka. These agents, which belong to the general class of perylene quinonoid pigments, have a long history of traditional medicinal agents especially in Asia. Hypocrellins are under extensive investigation as photosensitizing agents for photodynamic therapy (PDT). Hypocrellin compounds were selected as potential photosensitizers for PDT owing to their high quantum yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light absorption in the red spectral region, among other properties. The cellular uptake, evaluated by spectrofluorimetry and confocal laser scanning microscopy (CLSM) demonstrated that both HA and HB exhibited high and fast uptake and rapid internalization as revealed by their bio-distribution pattern. In addition, the present study employed both immunocytochemical and Western blot techniques to explore the photo-induced expression of apoptosis related proteins in NPC as well as other human carcinoma cells. Using spectrofluorimetry and CLSM we have determined the cellular fluorescence as a marker for the uptake of HA and HB. Co-staining with either HA or HB and fluorescent dyes specific for cell organelles revealed an intracellular localization of HA and HB in lysosomes other than mitochondria.
authors.affiliation: Department of Medical Sciences, National Cancer Centre, Singapore 169610.
authors.forename: Seyed Mohamed
authors.initials: SM
authors.lastname: Ali
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053477:Apoptotic Protease-Activating Factor 1; D031723:Bambusa / Q000737:chemistry; D015153:Blotting, Western; D003574:Cytochrome c Group / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007124:Immunoenzyme Techniques; D008247:Lysosomes / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019800:Phenol; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011809:Quinones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D004365:Drugs, Chinese Herbal; D017319:Photosensitizing Agents; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011809:Quinones; D051028:bcl-2-Associated X Protein; D019800:Phenol; D010569:Perylene; C048388:hypocrellin A; C064522:hypocrellin B