A Fluorescent Alkyllysophospholipid Analog Exhibits Selective Cytotoxicity Against the Hormone-Insensitive Prostate Cancer Cell Line PC3
A fluorescent analog of ET-18-OCH3, 1-O-(7’-N,N-dimethylamino-3’-pentadecanoyl-1’-naphthyl)-2-O-methyl-sn-glycerophosphocholine
(1), was synthesized and its bioactivity was screened against 12 human cancer cell lines. The bioactivity of 1 was found
to differ markedly from that of ET-18-OCH3. Growth of two prostate cell lines (PC3 and DU145) and a glioma cell line (U251) was
significantly affected by 1, with IC50 values of 2, 6, and 12 µM, respectively. Compound 1 was cytotoxic to PC3 cells by caspasedependent
apoptosis. The subcellular distribution of 1 differed from that reported for a phenyl-polyene analog of ET-18-OCH3; 1 was
found to be localized in the endoplasmic reticulum, mitochondria, and lysosomes but not in the plasma membrane or nucleus of PC3
cells. However, no differences in accumulation of 1 were found between PC3 and cells that were not affected by the compound, implying
that the selective PC3 cytotoxicity is a consequence of specific molecular components of PC3 cells.
Keywords: Antitumor ether lipids, edelfosine, fluorescent alkylphospholipid analog, naphthol-edelfosine, PC3 cells, selective toxicity.
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