Subcellular distribution and photocytotoxicity of aluminium phthalocyanines and haematoporphyrin derivative in cultured human meningioma cells.
The photocytotoxicity characteristics of aluminium phthalocyanine chloride (AIPc), aluminium phthalocyanine disulphonate (AlS2Pc), aluminium phthalocyanine tetrasulphonate (AlS4PC) and haematoporphyrin derivative (HpD) were compared using primary cultures of human meningioma cells. Cells were preincubated with the photosensitising agent for 16 h, then illuminated for 15 min with broad band red light (5 OW/cm2). The resultant cytotoxicity was assessed by tetrazolium (MTT) reduction 24 h later. AlPc was found to be 400, 10,000 and 250 times more potent that AlS2Pc, AlS4Pc and HpD, respectively, as an in vitro photosensitizing agent for meningioma cells. The subcellular localisation of AlPc, AlS2Pc, AlS4Pc and HpD in meningioma cells was determined by confocal laser scanning microscopy. None of the agents localized to the nucleus. The distribution of ALPc was quite diffuse through the cytoplasm. In contrast, AlS2Pc and AlS4Pc were localized vesicles suggestive of lysosomes, and HpD in membranous organelles distinct from mitochondria. AlPc and HpD were tested with five different meningioma samples and provided a range of IC50 values from 0.009 to 0.022 OM and from 3.5 to 6.5 OM, respectively. When the MTT assay with AlPc was performed 0, 24, 48 and 72 h after illumination, the mean IC50 values were 0.25, 0.037, 0.019 and 0.012 OM, respectively, indicating that the cytotoxic effect continued to increase up to 72 h. Cells were incubated with AlPc and HpD for different times up to 24 h before exposure to light. AlPc cytotoxicity was half-maximal with an incubation time of 8 h, whereas HpD cytotoxicity was half-maximal with an incubation time of 2 h, implying slower uptake kinetics for AlPc than for HpD. These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.
Malham
G M
GM
Department of Neurosurgery, Auckland Hospital, New Zealand.
Thomsen
R J
RJ
Finlay
G J
GJ
Baguley
B C
BC
D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D017324:Hematoporphyrin Derivative / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D054833:Isoindoles; D008579:Meningioma / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010860:Pigments, Biological / Q000494:pharmacology*; D011827:Radiation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D010860:Pigments, Biological; D017324:Hematoporphyrin Derivative; C013647:phthalocyanine