Effects of benzaldehyde on protein metabolism-of human cells cultivated in vitro.

The mechanism by which the antitumour agent benzaldehyde inhibits cell growth has been investigated. Human NHIK 3025 cells were synchronized by selection of mitotic cells and the protein content at various stages of the cell cycle was recorded by use of flow cytometry. In the presence of benzaldehyde (concentrations above 0.5 mM, approximately 50 micrograms/ml) the rate of protein accumulation was reduced to the same extent throughout the cell cycle. The rates of protein synthesis and protein degradation were measured by incorporation and release, respectively, of radioactively labelled valine in exponentially growing cells. It was found that benzaldehyde primarily reduced the rate of protein synthesis, while it induced only a very small effect (reduction) on the rate of protein degradation. When comparing the rate of cell-cycle progression with the rate of protein accumulation, it was found that the median interphase duration was equal to the protein doubling time even for concentrations of benzaldehyde giving a marked reduction in the rate of protein accumulation. Similar results have been observed on these cells using the specific protein synthesis inhibitor cycloheximide. However, the two drugs have different effects during mitosis, since benzaldehyde but not cycloheximide induces a specific mitotic inhibition. It is, therefore, possible that benzaldehyde inhibits the protein synthesis by a mechanism different from that of cycloheximide, a mechanism which simultaneously results in a specific mitotic inhibition. A hypothesis is proposed on the mechanism of action of benzaldehyde: that the drug might inhibit a process in the cells which activates enzymes. Such an effect might possibly entail a reduced protein synthesis as well as a prolonged mitosis. In addition, it might also count for the reported de-transforming activity of benzaldehyde on malignant cells.