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. MATERIALS AND 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 CONCLUSION: Digitonin enhances the antitumor effect of cisplatin against methylcholanthrene-induced rat sarcoma in vitro.