title: Mitochondria are the functional intracellular target for a photosensitizing boronated porphyrin.
abstract: A photosensitizing boron-containing porphyrin derivative denoted BOPP, which is selectively localised into mitochondria, has been tested on Namalwa cells, in each of two genetic configurations: rho+ cells containing normal mtDNA and mitochondrial respiratory functions, or rho0 cells lacking mtDNA and devoid of mitochondrial oxidative phosphorylation. After short-term cellular uptake for 18 h, BOPP (30 micrograms/ml) was not cytotoxic, but did show marked phototoxicity in Namalwa rho+ cells, concomitant with substantial reduction of mitochondrial respiratory activity. After long-term (3 days or more) exposure to BOPP without light, growth of Namalwa rho+ cells was inhibited at concentrations significantly above 30 micrograms/ml. At such concentrations BOPP was shown to have direct inhibitory effects on mitochondrial azide-sensitive respiration of p+ cells. By contrast, BOPP showed neither cytotoxic nor phototoxic effects in rho0 cells. These results indicate functional mitochondria to be a major cellular target in vivo after BOPP uptake and photoactivation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: A D
authors.initials: AD
authors.lastname: Munday
authors.forename: A
authors.initials: A
authors.lastname: Sriratana
authors.forename: J S
authors.initials: JS
authors.lastname: Hill
authors.forename: S B
authors.initials: SB
authors.lastname: Kahl
authors.forename: P
authors.initials: P
authors.lastname: Nagley
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology* / Q000633:toxicity; D004272:DNA, Mitochondrial / Q000502:physiology; D003905:Deuteroporphyrins / Q000494:pharmacology* / Q000633:toxicity; D004579:Electron Transport; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D011773:Pyruvates; D019289:Pyruvic Acid; D014407:Tumor Cells, Cultured; D014529:Uridine; D000098851:Carboranes
chemical_list: D001896:Boron Compounds; D004272:DNA, Mitochondrial; D003905:Deuteroporphyrins; D017319:Photosensitizing Agents; D011773:Pyruvates; D019289:Pyruvic Acid; D014529:Uridine; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes