Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture.
Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture.
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发表时间：
1997-04
期刊：
影响因子：
11.2
通讯作者：
J. Gaullier;K. Berg;Q. Peng;H. Anholt;P. Selbo;Li Wei Ma;J. Moan
中科院分区：
文献类型：
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作者：
J. Gaullier;K. Berg;Q. Peng;H. Anholt;P. Selbo;Li Wei Ma;J. Moan
用5-氨基乙酰丙酸（ALA）和ALA酯化成C1-C3和C6-C8链脂肪醇（ALA-酯）处理WiDr（直肠乙状结肠腺癌）、NHIK 3025（宫颈癌）和V79中国仓鼠成纤维细胞系的人肿瘤细胞。在人细胞系中，发现ALA与长链（C6-C8）醇的酯化使ALA的量减少30-150倍，所述ALA的量需要达到与非酯化ALA相同的原卟啉IX（PpIX）积累水平。长链ALA-酯在V79细胞中刺激PpIX形成的效率较低，即，相同量的PpIX由浓度比ALA低1-2.6倍的长链ALA-酯形成。短链ALA-酯（C1-C3）在所有细胞系中诱导的PpIX积累比ALA低5至10倍。高效液相色谱和荧光显微镜研究表明，ALA的酯化既不影响荧光卟啉物种的形成，也不影响其细胞内定位。发现由ALA-酯和ALA形成的PpIX在使细胞对光失活敏感方面同样有效。本研究结果表明，酯化ALA是一种新的和有前途的药物，用于光化学治疗癌症。
Human tumor cells of the lines WiDr (adenocarcinoma of the rectosigmoid colon), NHIK 3025 (carcinoma of the cervix), and V79 Chinese hamster fibroblasts were treated with 5-aminolevulinic acid (ALA) and ALA esterified to C1-C3 and C6-C8 chained aliphatic alcohols (ALA-esters). In the human cell lines, esterification of ALA with the long-chain (C6-C8) alcohols was found to reduce 30-150-fold the amount of ALA needed to reach the same level of protoporphyrin IX (PpIX) accumulation as with non-esterified ALA. The long-chained ALA-esters were less efficient in stimulating PpIX formation in V79 cells, i.e., the same amount of PpIX was formed by a 1-2.6-fold lower concentration of long-chained ALA-esters than with ALA. Short-chained ALA-esters (C1-C3) induced 5 to 10 times lower PpIX accumulation than ALA in all of the cell lines. High-performance liquid chromatography and fluorescence microscopic studies indicated that esterification of ALA has neither impact on the fluorescing porphyrin species formed nor impact on their intracellular localization. The PpIX formed from ALA-esters and ALA was found to be equally efficient in sensitizing cells to photoinactivation. The present results indicate that esterified ALAs are new and promising drugs for use in photochemotherapy of cancer.