Membrane phospholipids alter nutrient transport and drug toxicity in tumorigenic fibroblasts.
The phospholipid polar head group composition of LM cell plasma membranes was nutritionally altered by choline analogue supplementation. Phosphatidylcholine (PC), normally 60% of total phospholipid, was depleted by 60 to 90% in membranes from cells cultured with N, N'-dimethylethanolamine (DME), N-monomethylethanolamine (ME), and ethanolamine (E). Enrichment of LM cell membranes with choline analogues, such as DME-, ME-, and E-containing phospholipids, decreased the transport of [3H]thymidine, [3H]2-deoxy-D-glucose, and [14C]3-O-methylglucose. Conversely, no change in the transport of [3H] uridine or [14C]aminoisobutyric acid was observed. The toxicity of antineoplastic drugs such as 5-fluorouracil, but not daunorubicin, doxorubicin, or methotrexate, was enhanced threefold in cells enriched with phospholipid containing choline or DME as compared to ME or E. Arrhenius plots of Na+-K+-ATPase activity demonstrated a characteristic temperature at 29 degrees C in plasma membranes from choline-fed cells, while those from analogue-fed cells showed an additional break at 20 degrees C and had higher energies of activation below this temperature. In addition, choline analogue supplementation altered the protein composition of the plasma membrane. The results reported herein demonstrate that nutritional alteration of LM fibroblast plasma membrane phospholipid polar head group composition affects several transport processes and toxicity of some anticancer drugs.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002794:Choline / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D010743:Phospholipids / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000970:Antineoplastic Agents; D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D000254:Sodium-Potassium-Exchanging ATPase; D002794:Choline