Phosphatidylcholine Biosynthesis in the Neuroblastoma‐Glioma Hybrid Cell Line NG 108‐15: Stimulation by Phorbol Esters

Publisher Website
Google Scholar
Abstract
We have examined the effects of phorbol esters on phosphatidylcholine (PtdCho) metabolism in the neuroblastoma-glioma hybrid cell line NG108-15. 12-O-Tetradecanoylphorbol-13-acetate (TPA), 100 nM, stimulated twofold the incorporation of [3H]choline into PtdCho during 2 h of incubation at 37.degree. C. This effect of TPA was concentration dependent, exhibiting an EC50 of 24.5 .+-. 4.4 nM. The effect of TPA was also time dependent and became apparent only after a lag period of 15-30 min. TPA also decreased the incorporation of [3H]choline into water-soluble cellular constituents in a manner whose concentration and time-dependence paralleled the changes observed in Ptd-Cho content. HPLC analysis of this pool revealed that the level of its major (85-95%) constituent, [3H]phosphocholine, were decreased by 29 .+-. 5%, whereas those of [3H]glycerophosphocholine (0.5-2% of the pool) was increased by 84 .+-. 4%. PtdCho labeling was also stimulated when cells were pulse labeled with [3H]choline and chased in the presence of TPA. The incorporation of [3H]inositol, [14C]ethanolamine, or [14C]serine into phospholipids was not affected by TPA. The non-tumor-promoting compounds phorbol and 4.alpha.-phorbol-12,13-didecanoate (at 100 nM) were completely ineffective in modulating choline incorporation, whereas the biologically active analogs 4.beta.-phorbol-12,13-didecanoate and 4.beta.-phorbol-12,13-dibutyrate were as effective as TPA. We conclude that tumor-promoting phorbol esters can modulate PtdCho metabolism in neural-derived cells. The mechanisms mediating this effect and the possible involvement of PtdCho metabolism in normal signal transduction events and in the biological actions of tumor promoters are discussed.

This publication has 32 references indexed in Scilit: