Photosensitization by Photofrin II delivered to WI26VA4 SV40-transformed human fibroblasts by low density lipoproteins: inhibition of lipid synthesis and fatty acid uptake.
Irradiation with 365 nm light of Wi26VA4 SV40-transformed human fibroblasts cultured for 24 h in the presence of low density lipoproteins loaded with the anticancer porphyrin mixture Photofrin II resulted in a near complete inhibition of [14C]oleic acid incorporation into triacylglycerols, cholesteryl esters and phospholipids. More than 80% reduction of the fatty acid incorporation in all lipid classes was observed following an irradiation dose of 1 J/cm2. The activities of the respective acyltransferases, measured in vitro on cell homogenates, were also markedly diminished, but to a lesser extent than lipid synthesis from oleic acid. Moreover, oleic acid uptake by cells was strongly and rapidly reduced. It is suggested that the rapid inhibition of membrane phospholipid synthesis upon cell photosensitization, due to both a direct inactivation of acyltransferases and to a reduction of fatty acid utilization, could play an important role in the photocytotoxic effect of Photofrin II.
Biade
S
S
Laboratoire de Physico-Chimie de l'Adaptation Biologique INSERM U312, Paris, France.
Mazière
J C
JC
Mora
L
L
Santus
R
R
Morlière
P
P
Mazière
C
C
Salmon
S
S
Gatt
S
S
Dubertret
L
L
D002461:Cell Line, Transformed; D017323:Dihematoporphyrin Ether; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013539:Simian virus 40 / Q000235:genetics*; D014466:Ultraviolet Rays
D006415:Hematoporphyrins; D008055:Lipids; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D011838:Radiation-Sensitizing Agents; D019301:Oleic Acid; D017323:Dihematoporphyrin Ether