Effects of methylthiodeoxyadenosine and its analogs on in vitro invasion of rat ascites hepatoma cells and methylation of their phospholipids.
The relationship between tumor invasiveness in vitro and methylation of plasma membrane phospholipids was investigated. For this purpose, two hepatoma cell lines, C1-30 and LC-AH, were used which show specific penetration to below cultured monolayers of mesothelial cells from rat mesentery and endothelial cells from calf pulmonary artery, respectively. Methylthiodeoxyadenosine (MTA) and five of its analogs, difluoro-MTA, deoxyadenosine, sinefungin, phenylthiodeoxyadenosine and fluorophenylthiodeoxyadenosine, inhibited the invasion of the tumor cells without affecting their proliferation. This inhibition was associated with reduction in the incorporation of radioactivity of [methyl-3H]methionine into cellular phosphatidylethanolamine derivatives without changes in the labelings of RNA and DNA and carboxylmethylation of protein. These compounds also decreased the membrane fluidity of the tumor cells, measured by a steady-state fluorescence polarization method. Three other MTA analogs (fluorodideoxyadenosine, fluoroazidodideoxyadenosine and fluoroaminodideoxyuridine) did not affect the invasiveness of the tumor cells or alter their phospholipid methylation or membrane fluidity at concentrations that did not inhibit proliferation. These results suggest that the decrease in invasiveness of tumor cells by MTA and its analogs is due to alterations in the phospholipid composition and fluidity of the tumor cell membranes.
Kido
J
J
Department of Biochemistry, School of Dentistry, University of Tokushima.
Ashida
Y
Y
Shinkai
K
K
Akedo
H
H
Isoai
A
A
Kumagai
H
H
Inoue
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008745:Methylation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010743:Phospholipids / Q000378:metabolism; D013872:Thionucleosides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003839:Deoxyadenosines; D008563:Membrane Lipids; D010743:Phospholipids; D013872:Thionucleosides; D013873:Thionucleotides; C054301:5'-difluoromethylthioadenosine; C008500:5'-methylthioadenosine