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Enhanced cytotoxicity of photoexcited fullerene C60 and cisplatin combination against drug-resistant leukemic cells.

AIM
To evaluate the viability of leukemic cells sensitive (L1210S) and resistant (L1210R) to cisplatin, ROS production and free cytosolic Ca(2+) concentration under treatment with cisplatin or its combination with photoexcited fullerene C60.


METHODS
Cell viability was assessed by the MTT reduction assay. Light-emitting diode lamp (2.45 J/cm(2)) was used for photoexcitation of intracellular accumulated fullerene C60. Free cytosolic calcium concentration ([Ca(2+)]i) and ROS production in cells were estimated with the use of fluorescent probes Indo-1 and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively.


RESULTS
It is shown that viability of L1210R cells wasn't changed under treatment with cisplatin in concentration range 0.1-10 μg/ml. 50% and 30% decrease of L1210S cells were observed after 24 h of incubation with cisplatin at concentrations 5 and 1 μg/ml, respectively. Intensification of extranuclear cytotoxic effects (ROS production and [Ca(2+)]i increase) after treatment with 1 μg/ml was detected in L1210S, but not in L1210R cells. The most strongly pronounced increase of ROS production and [Ca(2+)]i in both L1210 cell lines was revealed in dynamics after combined treatment with cisplatin (1 μg/ml) and photoexcited fullerene C60 (10(-5) M) and was followed by decreased viability of not only L1210S, but of L1210R cells as well..


CONCLUSION
Combined treatment with photoexcited C60 and cisplatin allowed to decrease effective concentration of cisplatin against parental L1210 cells and to increase sensibility of resistant cells to the drug.