Effects of 3-Hydrogenkwadaphnin on intracellular purine nucleotide contents and their link to K562 cell death

Our previous studies have classified 3-Hydrogenkwadaphnin (3-HK), isolated from Dendrostellera lessertii (Thymelaeaceae), as a strong anti-proliferative agent that induces apoptosis among the treated leukemia cells mainly through IMP dehydrogenase inhibition. To disclose this point, we measured the intracellular ATP and GTP levels among K562 cells exposed to a single dose of 3-HK (7, 12 and 25 nM). The HPLC analyses of the 3-HK-treated cell lysates indicated a dose-dependent reduction in both GTP and ATP levels. The reduction of purine nucleotide levels was also associated with decreased activity of adenylosuccinate synthetase (AdSS) and enhanced level of cell death through apoptosis. However, the inhibitory effect of 3-HK was reversed by exogenous addition of guanosine with respect to GTP and partially with respect to ATP level. These data suggest that 3-HK targets a delicate regulatory system which governs the life/death fate of the cells partially through modulation of the GTP/ATP pool sizes.