Hormetic response of cultured normal and tumor cells to 2-aminotropone derivatives

We have recently reported that out of twenty benzo[b]cyclohept[e][1,4]oxazines and their S-analogs, and 2-aminotropone derivatives, 7-bromo-2-(4-hydroxyanilino) tropone and 4-isopropyl-2-(2-hydroxyanilino)tropone showed the highest tumor-specificity in human oral squamous cell carcinoma cell lines. To gain more insight into the anti-tumor actions of these compounds, whether they induce the growth stimulation effect observed at low concentrations, known as hormesis, was investigated using a total of ten human normal and tumor cultured cells. The tumor-specificity of both compounds became apparent 48 hours after the start of treatment of the cells with these compounds and reached a maximum level at 72 and 96 hours. On the other hand, their growth stimulatory effects were most prominent at 24 hours, especially in normal skin and lung fibroblasts, but rapidly disappeared with prolonged incubation time (48-96 hours). These data suggest the occurrence of a hormetic response only at restricted times and concentrations as has been previously reported, although the biological significance is yet to be elucidated.