Polar lipid remodeling and increased sulfatide expression are associated with the glioma therapeutic candidates, wild type p53 elevation and the topoisomerase-1 inhibitor, Irinotecan

Abstract

We report changes in gene and polar lipid expression induced by adenovirus-delivered wild-type (wt) p53 gene and chemotherapy of U87 MG glioblastoma cells, a treatment known to trigger apoptosis and cell cycle arrest. Sulfatides (sulfonated glycolipids) were most highly modulated by wild-type p53 treatment; however, no changes were observed in expression levels of mRNA for genes involved in sulfatide metabolism, indicating post-transcriptional control of sulfatide synthesis. Modulation of the aglycones of GD1 and GM1b was observed in wild-type p53-treated cells. The treatment also leads to an increase in phospholipids such as phosphatidyl inositols, phosphatidyl serines, phosphatidyl glycerols, and phosphatidyl ethanolamines, especially hydroxylated phospholipids. These dramatic changes in the composition of cellular glycolipids in response to p53 gene expression and cytotoxic chemotherapy treatment indicate the large role that they play in cell signaling. The use of the human glioma cell line U87 appears to be an excellent model system both in tissue culture and in intracranial murine xenograft models to further characterize the role of sulfatides in modulating glioma responsivity to therapeutic agents.

ESI–MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts

“…We have previously performed lipidomic analysis of GSCs and GBM cells (26-27). For the first time, we have applied lipidomics and MALDI-IMS to GSC xenografts.…”

Enhanced Antitumor Efficacy and Reduced Systemic Toxicity of Sulfatide-Containing Nanoliposomal Doxorubicin in a Xenograft Model of Colorectal Cancer

“…We have recently developed a novel liposomal carrier system that is composed of two lipids found in humans, sulfatide and 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE) [12], [13]. Under physiological pH, DOPE confers stability to sulfatide-containing liposomes (SCL) via its inhibitory effects on liposome fusion, as the incorporation of sulfatide into DOPE vesicles greatly enhances the stability of the liposomes formed, even in the presence of plasma, presumably due to the hydration of the negatively charged sulfate head-group of the glycosphingolipid [10].…”

Overexpression of ST6GalNAcV, a ganglioside-specific α2,6-sialyltransferase, inhibits glioma growth in vivo

“…We compared polar lipid changes in control U373MG cells and the two highest expressing ST6GalNAc transfectants (S8 and S25) by use of a detailed, sensitive, semiquantitative method using lipid extraction, one-step nano-liquid chromatography (nLC) separation, and high-resolution mass analysis (18,19). We observed significant modulation of specific gangliosides in the α-series pathway (Fig.…”

“…Polar lipids were extracted from cells and analyzed by nLC-MS as described (18,19) and detailed in SI Methods. Datadependent MS/MS was performed in the linear quadrupole ion trap (CID) during collection of the ICR time-domain data.…”