Structural Requirements of Dolichyl Phosphate as an Apoptosis Inducer

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Physiologically active dolichyl phosphate (dol-P) is known to induce apoptosis in human promonoblastic leukemia cells U937 and rat glioma C6 cells. The study on the relation between chemical structure and apoptosis-inducing ability of dol-P indicated that phosphate head group is one of the essential structures. This study investigated the significance of phosphate group by using two structurally related compounds, dolichyl sulfate (dol-S) and dolichyl diphenylphosphate (dol-DPP). Dol-S prepared from dolichol and N, N-dimethyl formamide sulfur trioxide complex, maintains a charge but lacks a phosphate group. Dol-DPP, prepared from dolichol and diphenyl chlorophosphate, retains a phosphate group but has no charge. Human promonoblastic leukemia cells U937 were subjected to the two dol-P analogues, and apoptosis-inducing ability was determined by studies on cell viability, cell morphology, DNA fragmentation, and activations of caspase-3 and 8. Dol-S induced apoptosis but dol-DPP did not. Moreover, dol-S was found to mediate apoptosis at only one-twentieth of the concentration of dol-P. These findings indicated that in dol-P-induced apoptosis, the charged group rather than the phosphate group was the required key structure for apoptosis induction.
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