Inhibition of phosphatidylcholine synthesis is not the primary pathway in hexadecylphosphocholine-induced apoptosis

Phospholipid Synthesis Participates in the Regulation of Diacylglycerol Required for Membrane Trafficking at the Golgi Complex

“…In the first case, the authors observed a decrease in secretion and suggested that PC was needed for protein transport at the Golgi. Of note, such a long incubation of CHO-MT58 cells at 40°C was demonstrated to reduced the DAG (45). In a similar study, the secretion was slowed down after blocking PC synthesis in macrophages.…”

Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex

“…1B ), providing further evidence for the relation between phospholipid metabolism and TAG/LD formation. This link is further strength- by guest, on May 11, 2018 www.jlr.org Downloaded from ies we did not observe an ER stress response in MT58 cells grown at the nonpermissive temperature ( 17,37 ). We could not prove the presence of autophagosome markers in PC-depleted cells (data not shown), thereby excluding the possibility of ER stress-induced ER-containing autophagosomes ( 36 ).…”

“…Furthermore, since DAG may also be converted in TAG by the release of FAs during the degeneration of PC, the overall effect of inhibiting PC synthesis in the MT58 cells on DAG levels in a particular membrane compartment is hard to predict. In earlier experiments, we already showed that total cellular DAG levels are decreased in PC-depleted MT58 cells ( 44 ). It might be interesting to know if the DAG concentration is specifi cally altered in the Golgi complex of PC-depleted MT58 cells as well.…”

Endoplasmic Reticulum Stress in the Proapoptotic Action of Edelfosine in Solid Tumor Cells

“…By contrast, class I lipids, such as ALPs, are characterized by their ability to form aggregates in which the polar/apolar interface curves away from the polar region and inhibit CCT (37,38). However, the similar patterns of phosphatidylcholine inhibition observed in both sensitive HeLa cells and drug-resistant Bcl-X L -transfected cells as well as in wild-type and drug-resistant bax (39). Likewise, farnesol-induced apoptosis has also been shown to be uncoupled from farnesolmediated inhibition of phosphatidylcholine biosynthesis (40).…”

“…Edelfosine has also been reported to inhibit phosphatidylcholine synthesis at a similar rate in both sensitive MCF-7 and resilient A549 tumor cell lines, A549 cell proliferation being unaffected (41). Hexadecylphosphocholine-induced apoptosis is prevented by the addition of either lysophosphatidylethanolamine or lysophosphatidylcholine, despite the fact that only lysophosphatidylcholine is able to attenuate the effect of the drug on phosphatidylcholine synthesis (39). This suggests that a more general disturbance in membrane structure, rather than a specific alteration in phosphatidylcholine metabolism, underlies ALP-induced apoptosis (39).…”