Polar lipid remodeling and increased sulfatide expression are associated with the glioma therapeutic candidates, wild type p53 elevation and the topoisomerase-1 inhibitor, irinotecan.
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.
He
Huan
H
National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, USA.
Nilsson
Carol L
CL
Emmett
Mark R
MR
Ji
Yongjie
Y
Marshall
Alan G
AG
Kroes
Roger A
RA
Moskal
Joseph R
JR
Colman
Howard
H
Lang
Frederick F
FF
Conrad
Charles A
CA
D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005732:Gangliosides / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D054794:Glycomics; D006801:Humans; D000077146:Irinotecan; D008055:Lipids / Q000032:analysis / Q000737:chemistry*; D051379:Mice; D010715:Phosphatidylglycerols / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D005732:Gangliosides; D008055:Lipids; D010715:Phosphatidylglycerols; D013433:Sulfoglycosphingolipids; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; D000077146:Irinotecan; D002166:Camptothecin