title: Synthesis of ether-linked analogues of lysophosphatidate and their effect on the proliferation of human epithelial cancer cells in vitro.
abstract: To investigate whether lysophosphatidate analogues of alkyllysophospholipids were antiproliferative we synthesized three new ether-linked analogues of lysophosphatidic acid and investigated their antiproliferative activity on epithelial cancer cell lines derived from different tissues. The antiproliferative effects of the compounds on MCF-7 and T47D (breast), A549 and A427 (lung), A498 (kidney), SK-N-SH and SK-N-MC (neuroblastoma), and DU145 (prostate) cells were compared with the ability of 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine, the archetypic alkyllysophospholipid, to inhibit the proliferation of all the cell lines. 1-O-Hexadecyl-2-O-methyl-sn-glycero-3-phosphate and 4-thiohexadecyl-3(S)-O-methoxybutane-4-phosphate were unable to inhibit the proliferation of any of the cells to any degree, while slightly enhancing the proliferation of DU145 cells. In contrast 4-O-hexadecyl-3(S)-O-methoxybutanephosphonate was a potent antiproliferative agent that was on the whole more active than 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine. Since 1-Oleoyl-2-lyso-phosphatidate (LPA) was non-mitogenic in all the cell lines except the neuroblastoma line SK-N-SH, it is unlikely that the inhibition of cell proliferation by 4-O-hexadecyl-3(S)-O-methoxybutanephosphonate was a consequence of perturbation of cellular response to the mitogenic effects of LPA.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Ashagbley
authors.forename: P
authors.initials: P
authors.lastname: Samadder
authors.forename: R
authors.initials: R
authors.lastname: Bittman
authors.forename: R K
authors.initials: RK
authors.lastname: Erukulla
authors.forename: H S
authors.initials: HS
authors.lastname: Byun
authors.forename: G
authors.initials: G
authors.lastname: Arthur
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D001943:Breast Neoplasms; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004987:Ethers; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms; D008175:Lung Neoplasms; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000633:toxicity; D008297:Male; D009447:Neuroblastoma; D063065:Organophosphonates; D011471:Prostatic Neoplasms; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004987:Ethers; D008246:Lysophospholipids; D063065:Organophosphonates