title: A fluorescent alkyllysophospholipid analog exhibits selective cytotoxicity against the hormone-insensitive prostate cancer cell line PC3.
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.
authors.forename: Pranati
authors.initials: P
authors.lastname: Samadder
authors.forename: Hoe-Sup
authors.initials: HS
authors.lastname: Byun
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, 754 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E 0J9. arthurg@ms.umanitoba.ca.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Arthur
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000498:Allyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology*
chemical_list: C000592577:1-O-(7'-N,N-dimethylamino-3'-pentadecanoyl-1'-naphthyl)-2-O-methyl-sn-glycerophosphocholine; D000498:Allyl Compounds; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D010742:Phospholipid Ethers; C026659:edelfosine; D015081:2-Naphthylamine; D020169:Caspases