Meso-substituted tetra-cationic porphyrins photosensitize the death of human fibrosarcoma cells via lysosomal targeting
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- 作者：Ricchelli ; Fernanda ; Franchi ; Lisa ; Miotto ; Giovanni ; Borsetto ; Lara ; Gobbo ; Silvano ; Nikolov ; Peter ; et. al.
- 关键词：C1 ; 5 ; 10 ; 15 ; 20-tetrakis-(4-N-methylpyridyl)-porphine ; DMEM ; Dulbecco’ ; s modified Eagle’ ; s medium ; FCCP ; carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone ; FCS ; foetal calf serum ; MAO ; monoaminooxidase ; PBS ; phosphate-buffered salin
- 刊名：The International Journal of Biochemistry and Cell Biology
- 出版年：2005
- 出版时间：February, 2005
- 年：2005
- 卷：37
- 期：2
- 页码：306-319
- 全文大小：439 K
文摘
In this paper we present a study on the intracellular localisation and the efficiency of cell photoinactivation of a series of derivatives of 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphine (C1), whose degree of lipophilicity was varied through replacement of one methyl group with an alkyl chain of various length. Human HT1080 fibrosarcoma cells exposed to the various C1 derivatives (0.25μM) for 24h and irradiated with increasing doses of red-light (0.45–27J/cm<sup>2sup>) were inactivated with different efficiencies. The efficiency of cell photoinactivation increased with the increasing length of the hydrocarbon tail and lipophilicity and correlated with the efficiency of the porphyrin accumulation into the cells. Despite the presence of positive charges, these porphyrins did localise rather selectively in lysosomes while mitochondrial localisation was not evident, as demonstrated by fluorescence microscopy studies. Studies on isolated mitochondria provided evidence that the porphyrin uptake and distribution in these organelles were not modulated by the transmembrane potential but were exclusively controlled by partitioning phenomena which might have prevented mitochondria localization in whole cells. Our findings demonstrated that these porphyrins entered the cells through the endocytotic pathway and were transported to lysosomes whose pH increased rapidly upon irradiation. Lysosomal damage did not cause any intracellular redistribution of the porphyrin and represented the primary event causing cell death, very likely via necrosis.