Modification of tumor cell sensitivity to antineoplastic agents lonidamine and bouvardin (NSC 259968) at elevated temperatures.
Lymphocytic leukemia P388 and Sarcoma-180 cells were exposed to various concentrations (0.01 mM to 0.04 mM) of lonidamine at 37 degrees C and 43 degrees C for 30 min and 60 min in vitro. Similarly combined effect of lonidamine and bouvardin on these tumor cells was also assessed at 37 degrees C and 43 degrees C. The effect was evaluated by comparing the rate of 3H-thymidine incorporation in treated cells to that of control cells. It was observed that at 37 degrees C lonidamine did not exert cytotoxic effect on P388 cells at prescribed time interval. Sarcoma-180 cells, however, showed significant sensitivity to the drug at 37 degrees C. Lonidamine exhibited greater cytotoxicity at 43 degrees C towards both P388 and Sarcoma-180 cells at 30 and 60 min exposure. Lonidamine also enhanced cytotoxicity of bouvardin in P388 and reversed the natural resistance of Sarcoma-180 cells to bouvardin at 37 degrees C.
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D006979:Hyperthermia, Induced; D007191:Indazoles / Q000627:therapeutic use*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000970:Antineoplastic Agents; D007191:Indazoles; D010456:Peptides, Cyclic; D011720:Pyrazoles; D014316:Tritium; C018234:bouvardin; D004247:DNA; C016371:lonidamine; D013936:Thymidine