A Fluorescent Alkyllysophospholipid Analog Exhibits Selective Cytotoxicity Against the Hormone-Insensitive Prostate Cancer Cell Line PC3

作者：Samadder Pranati; Byun Hoe Sup; Bittman Robert^*; Arthur Gilbert

来源：Anti-Cancer Agents in Medicinal Chemistry, 2014, 14(4): 528-538.

DOI：10.2174/1871520614666140309223603

• Antitumor ether lipids
• edelfosine
• fluorescent alkylphospholipid analog
• naphthol-edelfosine
• PC3 cells
• selective toxicity

A fluorescent analog of ET-18-OCH3, 1-O-(7%26apos;-N,N-dimethylamino-3%26apos;-pentadecanoyl-1%26apos;-naphthyl)-2-O-methyl-sn-glycero-phosphocholine (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 mu M, respectively. Compound 1 was cytotoxic to PC3 cells by caspase-dependent 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.

• 出版日期2014-5