nsc-259-968 and Leukemia-P388

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

Bouvardin, a new antineoplastic plant product, inhibits macromolecular synthesis in P388 cells in a dose-dependent manner. At the same concentration of bouvardin, protein synthesis was inhibited to a greater extent than the synthesis of DNA and RNA. There was a reversal of inhibition of both DNA and RNA synthesis after the cells were washed free of bouvardin. However, there was partial reversal of inhibition of protein synthesis when the cells were washed free of the drug.

Topics: Animals; Antineoplastic Agents, Phytogenic; Depression, Chemical; DNA, Neoplasm; Dose-Response Relationship, Drug; Leucine; Leukemia P388; Leukemia, Experimental; Mice; Mice, Inbred DBA; Neoplasm Proteins; Peptides, Cyclic; RNA, Neoplasm; Thymidine; Uridine

A comparative study of cytostatic combinations was carried out in early and advanced murine leukaemia P388 by using the new protein synthesis inhibitor bouvardin (BVD) along with the known anticancer drugs vincristine (VCR) and cis-diamminedichloroplatinum (DDP). The results indicate that the combination of BVD with DDP enhances the antineoplastic activity in comparison with single-agent therapy in early leukaemia. However, BVD could not indicate its superiority by way of tumour cell killing in three drug combinations, when administered with VCR and/or DDP, against advanced leukaemia.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Leukemia P388; Leukemia, Experimental; Male; Mice; Peptides, Cyclic; Time Factors; Vincristine

The induction of complete resistance to adriamycin in L1210 leukemia was accomplished after 10 transplant generations. The adriamycin-resistant subline showed cross-resistance to vincristine and bouvardin. It was sensitive to methotrexate; this was observed by a 50% increase in life span compared to the life span of untreated control animals.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line; Doxorubicin; Drug Resistance; Leukemia L1210; Leukemia P388; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Peptides, Cyclic; Vincristine

The plant product Bouvardin (BVD; NSC 259968) exhibited high activity against P388 murine leukemia and B16 melanoma, but it was not effect against various other tumor models. BVD inhibited the synthesis of all the macromolecules, namely protein, DNA and RNA, in P388 cells in vitro. Protein synthesis was most susceptible to the drug action. However, DNA and RNA synthesis were affected to a lesser extent. Further studies revealed that BVD did not inhibit protein degradation in P388 leukemia cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; DNA, Neoplasm; Leukemia P388; Leukemia, Experimental; Melanoma; Mice; Neoplasm Proteins; Neoplasms, Experimental; Peptides, Cyclic; RNA, Neoplasm