Relationship between amine-carboxyboranes and TNFα for the regulation of cell growth in different tumor cell lines

The amine-carboxyboranes were shown to be synergistic with tumor necrosis factor alpha (TNFα) in cytotoxicity and inhibition of DNA synthesis in select types of cancer cells depending on the presence of a TNFα high affinity receptor on the membrane of the cell. Initially both TNFα and the amine-carboxyboranes reduce the influx of calcium but later cause a significant increase intracellularly. This influx is not linked with the amine-carboxyborane activating the calcitonin receptor in the tumor cells. Neither the agents nor TNFa directly inhibits DNA topoisomerase II activity but both did cause decreased phosphorylation of the enzyme by protein kinase C (PKC). The two agents caused synergistic inhibition. This event correlated with increased DNA protein linked breaks, DNA fragmentation and cell death. These protein linked breaks are additive with etoposideʹs effects but the latter agentʹs mechanism is different than phosphorylation of topoisomerase II. There was no evidence that the DNA fragmentation was caused hy a calcium induced endonuclease enzyme in these cancer cells. The low-molecular weight amine-carboxyboranes appear to play an identical function as TNFα in its role to cause DNA breaks and fragmentation to cause apoptosis. © 1998 Elsevier, Paris.