Biade S, Mazière J C, Mora L, Santus R, Morlière P, Mazière C, Salmon S, Gatt S, Dubertret L
Laboratoire de Physico-Chimie de l'Adaptation Biologique INSERM U312, Paris, France.
Photochem Photobiol. 1992 Jan;55(1):55-61. doi: 10.1111/j.1751-1097.1992.tb04209.x.
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.
在含有负载抗癌卟啉混合物二血卟啉醚的低密度脂蛋白的情况下培养24小时的Wi26VA4 SV40转化人成纤维细胞,用365nm光照射,导致[14C]油酸掺入三酰甘油、胆固醇酯和磷脂几乎完全受到抑制。照射剂量为1J/cm2后,观察到所有脂质类别中脂肪酸掺入减少了80%以上。在细胞匀浆上体外测量的相应酰基转移酶的活性也明显降低,但程度小于油酸的脂质合成。此外,细胞对油酸的摄取强烈且迅速减少。有人提出,细胞光致敏后膜磷脂合成的快速抑制,由于酰基转移酶的直接失活和脂肪酸利用的减少,可能在二血卟啉醚的光细胞毒性作用中起重要作用。