Distribution and subcellular localization of a water-soluble hematoporphyrin-platinum(II) complex in human bladder cancer cells.
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.
Institute of Inorganic Chemistry, University of Regensburg, 93040 Regensburg, Germany. christian.lottner@exfor.uni-regensburg.de
Christian
C
Lottner
Ruth
R
Knuechel
Guenther
G
Bernhardt
Henri
H
Brunner
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006415:Hematoporphyrins / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000627:therapeutic use; D010984:Platinum / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry / Q000627:therapeutic use*; D018874:Spheroids, Cellular; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006415:Hematoporphyrins; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; C493894:diammine(7,12-bis(1-(polyethyleneglycol-750-monomethylether-1-yl)ethyl)-3,8,13,17-tetramethylporphyrin-2,18-dipropionato)platinum(II); D010984:Platinum