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Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid
- Source :
- Biochimica et biophysica acta. 1771(1)
- Publication Year :
- 2006
-
Abstract
- Cyclic phosphatidic acid (1-acyl-sn-glycerol-2,3-cyclic phosphate; cPA) is a naturally occurring analog of lysophosphatidic acid (LPA) with a variety of distinctly different biological activities from those of LPA. In contrast to LPA, a potent inducer of tumor cell invasion, palmitoyl-cPA inhibits FBS- and LPA-induced transcellular migration and metastasis. To prevent the conversion of cPA to LPA we synthesized cPA derivatives by stabilizing the cyclic phosphate ring; to prevent the cleavage of the fatty acid we generated alkyl ether analogs of cPA. Both sets of compounds were tested for inhibitory activity on transcellular tumor cell migration. Carba derivatives, in which the phosphate oxygen was replaced with a methylene group at either the sn-2 or the sn-3 position, showed much more potent inhibitory effects on MM1 tumor cell transcellular migration and the pulmonary metastasis of B16-F0 melanoma than the natural pal-cPA. The antimetastatic effect of carba-cPA was accompanied by the inhibition of RhoA activation and was not due to inhibition of the activation of LPA receptors.
- Subjects :
- RHOA
Lung Neoplasms
Lysophospholipids
Phosphatidic Acids
Antineoplastic Agents
Biology
Article
Enzyme activator
chemistry.chemical_compound
Mice
Cell Movement
Cell Line, Tumor
Lysophosphatidic acid
Animals
Humans
heterocyclic compounds
Transcellular
Neoplasm Metastasis
Molecular Biology
Melanoma
chemistry.chemical_classification
Fatty acid
Cell Biology
Phosphatidic acid
Phosphate
Xenograft Model Antitumor Assays
Rats
Enzyme Activation
chemistry
Biochemistry
biology.protein
cardiovascular system
lipids (amino acids, peptides, and proteins)
biological phenomena, cell phenomena, and immunity
rhoA GTP-Binding Protein
Subjects
Details
- ISSN :
- 00063002
- Volume :
- 1771
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta
- Accession number :
- edsair.doi.dedup.....2b80d5c21601d83e1b9a3b408cf7185f