Modifying effect of cinnamaldehyde and cinnamaldehyde derivatives on cell inactivation and cellular uptake of cis-diamminedichloroplatinum(II) in human NHIK 3025 cells

Abstract

The effect of cinnamaldehyde and various cinnamaldehyde derivatives on cell inactivation induced by cis-diamminedichloroplatinum(II) (cis-DDP) was investigated using human NHIK 3025 cells in culture. Cell inactivation was measured as a loss in the ability of single cells to give rise to macroscopic colonies following drug treatment. It was found that cinnamaldehyde and alpha-chlorocinnamaldehyde potentiated the cell-inactivating effect when used simultaneously with cis-DDP without increasing the amount of cell-associated platinum. In contrast, a protective effect with respect to cell inactivation was found when cells were treated with cis-DDP in combination with hydrocinnamaldehyde or alpha-methylcinnamaldehyde. At higher concentrations (greater than 1 mM) all cinnamaldehyde derivatives reduced cellular uptake of cis-DDP. Therefore, while protection from cis-DDP-induced cell inactivation involves reduced platinum uptake, potentiation by cinnamaldehyde and cinnamaldehyde derivatives does not seem to be due to an increase in intracellular platinum. We propose that cinnamaldehyde may compete with cis-DDP in nucleophilic addition reactions involving intracellular sulfhydryls.