title: Aminolevulinic acid derivatives-based photodynamic therapy in human intra- and extrahepatic cholangiocarcinoma cells.
abstract: Hexyl-aminolevulinic acid (HALA) was compared with aminolevulinic acid (ALA) in terms of improving ALA-based photodynamic therapy (PDT) for human intra- and extrahepatic cholangiocarcinoma (CCA) HuCC-T1 and SNU1196 cells. Because of the different uptake mechanisms of HALA, a relatively higher amount of protoporphyrin IX (PpIX) was induced in the both CCA cell types at low concentrations of HALA. Furthermore, higher expression of porphobilinogen deaminase, coproporphyrinogen III oxidase, and protoporphyrinogen oxidase, the key enzymes for synthesizing PpIX in the heme biosynthetic pathway, facilitated the exuberant generation of PpIX in HuCC-T1 cells. PpIX accumulation with ALA was markedly different between the two CCA cell types. Even at lower concentrations of ALA, SNU1196 cell successfully synthesized PpIX, due to the higher expression of the ALA transporter, mammalian H (+)/peptide co-transporter PEPT1. Considering the difference of PEPT1 or key enzyme expression, HALA could be a very effective substitute for ALA in doing PDT for cure of CCA.
authors: Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors: Chung-Wook
authors: CW
authors: Chung
authors: Cy Hyun
authors: CH
authors: Kim
authors: Hye Myeong
authors: HM
authors: Lee
authors: Do Hyung
authors: DH
authors: Kim
authors: Tae-Won
authors: TW
authors: Kwak
authors: Kyu-Don
authors: KD
authors: Chung
authors: Young-Il
authors: YI
authors: Jeong
authors: Dae Hwan
authors: DH
authors: Kang
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000074011:Peptide Transporter 1; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011524:Protoporphyrins / Q000378:metabolism; D027981:Symporters / Q000235:genetics
chemical_list: D000074011:Peptide Transporter 1; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C082186:SLC15A1 protein, human; D027981:Symporters; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C419924:5-aminolevulinic acid hexyl ester
keywords: 5-Aminolevulinic acid; Cholangiocarcinoma; Hexyl ester 5-aminolevulinic acid; Key enzyme in heme synthesis; PEPT1; Photodynamic therapy