Antitumoral activity of a sulphur-containing platinum complex with an acidic pH optimum.
Platinum complexes are essential tools for cancer treatment despite their toxic side effects. Here we describe a new platinum complex with sulphurs as complexing atoms (thioplatin).


OBJECTIVE
To demonstrate that the antitumoral activity of a new sulphur-containing platinum compound (thioplatin) depends on a slightly acidic pH.


METHODS
Platinum uptake by tumour cells and interaction with DNA was determined at slightly acidic or alkaline pH. To demonstrate low in vivo toxicity the effects of thioplatin on body weight, blood urea nitrogen, white blood cell count and the histopathological appearance of small intestines and kidneys were evaluated at doses that displayed antitumoral effects against human small-cell lung cancer and human colorectal cancer xenotransplants in nude mice.


RESULTS
The slightly acidic pH optimum of thioplatin was proven by the altered electrophoretic mobility of plasmid DNA, quantitation of the platinum content in the DNA of tumour cells and cytotoxicity studies. Thioplatin displayed antitumoral activity without severe side effects such as weight loss, renal ischaemia, destruction of villi in the small intestine or leukopenia as observed at comparable doses of cisplatin. Furthermore, probably due to its lipophilic nature, thioplatin was taken up readily even by cisplatin-resistant cells. In vivo studies with human tumour xenografts in nude mice showed a therapeutic index of thioplatin five to ten times higher than that of cisplatin.
Amtmann
E
E
German Cancer Research Centre, Department D0600, Heidelberg. e.amtmann@dkfz-heidelberg.de
Zöller
M
M
Wesch
H
H
Schilling
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003432:Cross-Linking Reagents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007939:Leukemia L1210 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy; D013457:Sulfur Compounds / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D013457:Sulfur Compounds; C431426:thioplatin; D002945:Cisplatin