Digitonin enhances the anti-tumor effect of cisplatin against methylcholanthrene-induced rat sarcoma cells in vitro.
BACKGROUND
This study was designed to evaluate cellular uptake and cytotoxicity of cisplatin in methylcholanthrene (MCA)-induced rat sarcoma cells when used in combination with a detergent, digitonin.


METHODS
In the cellular intake study, after MCA sarcoma cells (10(7)) were treated with cisplatin alone (50 micrograms/ml) and with cisplatin (50 micrograms/ml) in combination with digitonin at 20 microM and 50 microM, the cells were washed twice with PBS and the platinum levels were measured by flameless atomic spectrometry. For the anti-tumor effect MCA sarcoma cells (10(3)) were seeded in cell culture dishes and loaded for 10 minutes with PBS, digitonin (5 microM), cisplatin (5 micrograms/ml) or a combination of cisplatin (5 micrograms/ml) and digitonin (5 microM). The cells were then washed and incubated for 72 hours. Bromodeoxyuridine uptake was measured with an ELISA system for determining viable cells counts.


RESULTS
Cell platinum levels were significantly elevated in proportion to the increase of digitonin (p < 0.0001). The number of viable cells was significantly decreased with, the combined cisplatin (5 micrograms/ml)--digitonin (5 microM) treatment (p < 0.0001


CONCLUSIONS
Digitonin enhances the antitumor effect of cisplatin against methylcholanthrene-induced rat sarcoma in vitro.
Tanaka
T
T
Department of Surgery I, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. toshik@po.cc.yamaguchi-u.ac.jp
Kaneda
Y
Y
Li
T S
TS
Matsuoka
T
T
Zempo
N
N
Esato
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001693:Biological Transport, Active; D002463:Cell Membrane Permeability; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology*; D004357:Drug Synergism; D008748:Methylcholanthrene; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D003902:Detergents; D008748:Methylcholanthrene; D004072:Digitonin; D002945:Cisplatin