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

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

Volume: 14 Issue: 4

Author(s): Pranati Samadder, Hoe-Sup Byun, Robert Bittman and Gilbert Arthur

Affiliation:

Keywords: Antitumor ether lipids, edelfosine, fluorescent alkylphospholipid analog, naphthol-edelfosine, PC3 cells, selective toxicity.

Abstract: 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.

Cite this article as:

Samadder Pranati, Byun Hoe-Sup, Bittman Robert and Arthur Gilbert, A Fluorescent Alkyllysophospholipid Analog Exhibits Selective Cytotoxicity Against the Hormone-Insensitive Prostate Cancer Cell Line PC3, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (4) . https://dx.doi.org/10.2174/1871520614666140309223603