nsc-259-968 and Sarcoma-180

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.

Topics: Animals; Antineoplastic Agents; DNA; Drug Resistance; Hyperthermia, Induced; Indazoles; Leukemia P388; Mice; Neoplasms, Experimental; Peptides, Cyclic; Pyrazoles; Sarcoma 180; Thymidine; Tritium

The cytotoxic effect of bouvardin (BVD) a protein synthesis inhibitor was studied separately and in combination with verapamil (VRP), a vasodilator and hyperthermia (43 degrees C) against Sarcoma 180 (S 180) and Ehrlich ascites carcinoma (EAC) tumour cells in vitro. S 180 cells exhibited natural resistance to hyperthermia and BVD, whereas EAC tumour cells were found to be sensitive. VRP alone did not show cytotoxicity to either tumour cells. A combination of BVD and VRP at an elevated temperature resulted in a greater cell kill in the EAC tumour cell line whereas the natural resistance of S 180 tumour cells to the drug BVD and hyperthermia was circumvented by combination with VRP. Combination of BVD, hyperthermia and VRP resulted in greater cell kill, compared to separate treatment with the single agents. The cytotoxicity was evaluated by comparing the inhibition of incorporation of 3H-thymidine in treated cells to that in untreated cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Cell Line; Cell Membrane Permeability; Combined Modality Therapy; DNA; Drug Resistance; Drug Synergism; Hyperthermia, Induced; Peptides, Cyclic; Sarcoma 180; Verapamil

Reversal of natural resistance to bouvardin (NSC 259968) has been attained in vitro and in vivo, by the calcium influx blocker verapamil in sarcoma 180 cells insensitive to bouvardin. Verapamil increased the in vitro lethality of the tumor cells following exposure with cells for 1 and 3 h as a result of the cytotoxic effect of bouvardin. Similar results were observed in vivo when the tumor cells were exposed to verapamil and then treated with bouvardin, showing a significant percent increase in the lifespan to 30% and 45%. This suggested that this calcium channel blocker had interacted with tumor cell membrane to modulate the response of the cells, and make them more amenable to the drug action.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line; Drug Resistance; Mice; Peptides, Cyclic; Sarcoma 180; Verapamil

Sarcoma-180 (S-180) tumor cells grown in Swiss mice displayed natural resistance to Bouvardin (NSC 259968) when administered alone in a single dose or in multiple doses. Hyperthermia treatment (43 degrees C for 1 hr) alone did not show any tumor growth reduction. However, the drug combined with hyperthermia markedly reduced tumor growth suggesting that hyperthermia alters the natural resistance of S-180 cells to Bouvardin.

Topics: Animals; Antineoplastic Agents, Phytogenic; Combined Modality Therapy; Drug Evaluation, Preclinical; Drug Resistance; Hyperthermia, Induced; Mice; Mice, Inbred Strains; Peptides, Cyclic; Sarcoma 180