Author(s): JeanMichel Gauffier
Human tumor cells of the lines WiDr (adenocarcinoma of the rectosig mold colon), NIIIK 3025 (carcinoma of the cervix), and V79 Chinese hamster fibroblasts were treated with 5-aminolevulinic acid (ALA) and ALA esterifled to [email protected] and C6-C8 chained aliphatic alcohols (ALA esters). In the human cell lines, esterification of ALA with the long-chain ([email protected])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-esterifled ALA. The long-chained ALA-esters were less effi dent in stimulating PpIX formation in V79 cells, i.e., the same amount of PpIX was formed by a 1â€”2.6-foldlower concentration of long-chained ALA-esters than with ALA. Short-chained ALA-esters (C1-C3)induced S 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.