Melanoma tumors acquire a new phospholipid metabolism phenotype under cystemustine as revealed by high-resolution magic angle spinning proton nuclear magnetic resonance spectroscopy of intact tumor samples.
N'-[2-chloroethyl]-N[2-(methylsulfonyl) ethyl]-N'-nitrosourea (cystemustine),a chloroethylnitrosourea antineoplastic drug, provokes cellular proliferation inhibition and redifferentiation, but there was no cell death in B16 melanoma tumors. Because the phospholipid (Plp) metabolism is tightly involved in tumor growth regulation and tumor cell survival, we tested the hypothesis that melanoma tumors undergo adaptive Plp metabolism changes to survive treatment. Measurements of Plp derivatives were performed using a novel proton nuclear magnetic resonance Spectroscopy application using magic angle spinning on intact tumor tissue samples. Phosphatidylcholine levels were obtained from one-dimensional spectra, and relative levels of choline- and ethanolamine-containing compounds were derived from two-dimensional spectra (total correlation spectroscopy sequence). Two major findings emerged from this study: (a) during tumor growth inhibition, there was a transient accumulation of choline, glycerophosphocholine, and glycerophosphoethanolamine and a sustained increase in phosphocholine and phosphoethanolamine, whereas phosphatidylcholine levels remained unchanged; and (b) during tumor growth recovery, only phosphocholine and phosphoethanolamine remained elevated. Therefore, cystemustine-treated B16 melanoma tumors acquire a new Plp metabolism phenotype, a mechanism that could participate in tumor cell redifferentiation and/or survival.
Morvan
Daniel
D
Institut National de la Santé et de la Recherche Médicale U 484, Clermont-Ferrand, France. morvan@inserm484.u-clermont1.fr
Demidem
Aicha
A
Papon
Janine
J
De Latour
Monique
M
Madelmont
Jean Claude
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010767:Phosphorylcholine / Q000378:metabolism; D011522:Protons
D000970:Antineoplastic Agents; D004983:Ethanolamines; D009607:Nitrosourea Compounds; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011522:Protons; D010767:Phosphorylcholine; C002449:glycerophosphoethanolamine; C005448:phosphorylethanolamine; C051263:N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea; D002794:Choline