Uptake of the carborane derivative of cholesteryl ester by glioma cancer cells is mediated through LDL receptors.
OBJECTIVE
This study was to elucidate the mechanism of cellular uptake of cholesteryl 1,12-dicarba-closo-dodecaboranel-carboxylate (BCH), a new anti-cancer carborane derivative of cholesteryl ester, by glioma cancer cells.


METHODS
BCH (solubilized with liposomal formulation) was incubated with SF-763 and SF-767 glioma cell lines in the presence of different amounts of monoclonal anti-LDL receptor antibody for cellular uptake studies. Various amounts of lipoprotein deficient serum (LPDS) were also used during the uptake. The effect of calcium ion and low temperature on BCH uptake were investigated. In addition, the transfer of BCH from liposomes to low-density lipoprotein (LDL) particles was determined through gradient ultracentrifugation.


RESULTS
BCH uptake by these glioma cells was significantly inhibited by the monoclonal antibody. The uptake by both cell lines was reversely correlated with the amount of LPDS. The presence of calcium ion promoted the BCH uptake, whereas the low temperature decreased the BCH uptake. After 16 h incubation, about 46% of BCH was transferred from liposomes to LDL particles.


CONCLUSIONS
These results strongly suggested that the cellular uptake of BCH (in liposomal formulation) by SF-763 and SF-767 glioma cell lines is mediated through LDL receptors.
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA.
Guangliang
G
Pan
Svein
S
Oie
D Robert
DR
Lu
D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology; D001896:Boron Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005910:Glioma; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008081:Liposomes; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001896:Boron Compounds; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008081:Liposomes; D011973:Receptors, LDL; C496891:cholesteryl 1,12-dicarba-closo-dodecaboranel-carboxylate; D002118:Calcium