Distribution and subcellular localization of a water-soluble hematoporphyrin–platinum(II) complex in human bladder cancer cells

• Published in: Cancer letters Vol. 215; no. 2; pp. 167 - 177
• Main Authors: Lottner, Christian, Knuechel, Ruth, Bernhardt, Guenther, Brunner, Henri
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 25.11.2004; Elsevier Limited
• Subjects: Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Bladder cancer; Cancer therapies; Cell Line; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA, Neoplasm - metabolism; Drug Screening Assays, Antitumor; Hematoporphyrins - metabolism; Hematoporphyrins - therapeutic use; Humans; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - metabolism; Organoplatinum Compounds - therapeutic use; Photodynamic therapy; Photosensitizing Agents - metabolism; Photosensitizing Agents - therapeutic use; Platinum; Platinum - metabolism; Porphyrins - chemistry; Porphyrins - therapeutic use; Porphyrin–platinum complex; Proteins; Selective accumulation; Spheroids, Cellular; Tissue Distribution; Tumors; Urinary Bladder - metabolism; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism; Germany; PDT; Chemotherapy; Photodynamic therapy; PEG; Selective accumulation; M-VAC; DMF; Porphyrin–platinum complex; Bladder cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2004.06.035

The water-soluble porphyrin–platinum complex diammine{7,12-bis[1-(polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato}platinum(II) (PEG-HPPt) was studied with respect to cellular accumulation, subcellular localization, behavior in 3D-cell aggregates and degree of DNA platination on the low-differentiated J82 cells, a model of invasive bladder cancer, and UROtsa, a normal urothelial cell line. Accumulation studies with 2D and spheroid cell cultures revealed that the concentration of PEG-HPPt was 1.7-times higher in J82 cancer cells than in UROtsa cells. Despite its high molecular weight, penetration of PEG-HPPt was not restricted to the peripheral cells of the spheroids. Fluorescence microscopic analysis showed that PEG-HPPt was localized in essential cellular targets of photodynamic therapy. DNA platination in J82 and UROtsa cells was higher by PEG-HPPt than by cisplatin, whereas there was no significant difference between the two cell lines.