Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several possible mechanisms of the synergistic interactions of IL-1 alpha and VP-16 against A375-C6 human melanoma cells were investigated. Studies indicate that IL-1 alpha did not increase topoisomerase II-dependent VP-16-mediated DNA damage, nor did IL-1 alpha inhibit the repair of VP-16-induced DNA damage in these cells. Furthermore, IL-1 alpha by itself or in combination with VP-16 did not cause significant fragmentation of cellular DNA into oligomers, indicating programmed cell death (apoptosis) was not involved in the mechanism of synergy. In contrast, an IL-1-specific receptor antagonist significantly decreased IL-1 alpha toxicity toward the melanoma cells and nearly eliminated the synergistic interactions of IL-1 alpha with VP-16. These results strongly indicate that synergism of IL-1 alpha with VP-16 was dependent upon an IL-1-receptor-mediated processes. DNA-strand breakage was unlikely to be a primary intracellular target for IL-1 alpha cytotoxicity and synergism with VP-16.
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PMID:Synergistic interactions of etoposide and interleukin-1 alpha are not due to DNA damage in human melanoma cells. 842 27

The recurrence of pulmonary metastases resistant to salvage chemotherapy continues to be a major problem in osteosarcoma patients. Our goal is to identify novel combinations of biologic response modifiers plus chemotherapeutic agents that can be translated into clinical trials. Response rates of relapsed osteosarcoma patients to etoposide have been extremely low. The present investigation demonstrated that IL-1 alpha dramatically increased the sensitivity of MG-63, SAOS-2, and TE-85 osteosarcoma cells to etoposide when the two agents were used simultaneously. The cytostatic activity of 1 microM etoposide was increased from 35 to 70%, 30 to 65%, and 4 to 90%, respectively, by 5.0 U/ml IL-1 alpha. Analysis using the colony-forming assay to quantify cytotoxicity showed that the percentage of cell survival following exposure to etoposide decreased from 0.81 to 0.56, 0.55 to 0.2, and 0.4 to 0.05 when the combination treatment was used. Increased sensitivity was not seen when etoposide treatment preceded IL-1 alpha treatment. IL-1 alpha also increased the sensitivity of these cells to doxorubicin but not to cisplatin or topotecan. The mechanism of this enhanced activity is independent of p-glycoprotein, drug-uptake, or effects on topoisomerase II.
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PMID:Interleukin-1 alpha increases the cytotoxic activity of etoposide against human osteosarcoma cells. 1241 17