| RRC ID |
44492
|
| Author |
Yamamoto M, Fujita H, Katase N, Inoue K, Nagatsuka H, Utsumi K, Sasaki J, Ohuchi H.
|
| Title |
Improvement of the efficacy of 5-aminolevulinic acid-mediated photodynamic treatment in human oral squamous cell carcinoma HSC-4.
|
| Journal |
Acta Med Okayama
|
| Abstract |
Ever since protoporphyrin IX (PpIX) was discovered to accumulate preferentially in cancer cells after 5-aminolevulinic acid (ALA) treatment, photodynamic treatment or therapy (PDT) has been developed as an exciting new treatment option for cancer patients. However, the level of PpIX accumulation in oral cancer is fairly low and insufficient for PDT. Ferrochelatase (FECH) and ATP-binding cassette transporter G2 (ABCG2) are known to regulate PpIX accumulation. In addition, serum enhances PpIX export by ABCG2. We investigated here whether and how inhibitors of FECH and ABCG2 and their combination could improve PpIX accumulation and PDT efficacy in an oral cancer cell line in serum-containing medium. ABCG2 inhibitor and the combination of ABCG2 and FECH inhibitors increased PpIX in the presence of fetal bovine serum (FBS) in an oral cancer cell line. Analysis of ABCG2 gene silencing also revealed the involvement of ABCG2 in the regulation of PpIX accumulation. Inhibitors of FECH and ABCG2, and their combination increased the efficiency of ALA-PDT even in the presence of FBS. ALA-PDT-induced cell death was accompanied by apoptotic events and lipid peroxidation. These results suggest that accumulation of PpIX is determined by the activities of ABCG2 and FECH and that treatment with a combination of their inhibitors improves the efficacy of PDT for oral cancer, especially in the presence of serum.
|
| Volume |
67(3)
|
| Pages |
153-64
|
| Published |
2013-1-1
|
| DOI |
10.18926/AMO/50408
|
| PMID |
23804138
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics
Amino Acid Chloromethyl Ketones / pharmacology
Aminolevulinic Acid / pharmacology*
Apoptosis / drug effects
Blood Proteins / pharmacology
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Caspase Inhibitors / pharmacology
Cell Line, Tumor
Deferoxamine / pharmacology
Ferrochelatase / antagonists & inhibitors
Gene Silencing
Humans
Lipid Peroxidation / drug effects
Mouth Neoplasms / drug therapy*
Mouth Neoplasms / metabolism
Mouth Neoplasms / pathology
Neoplasm Proteins / genetics
Photochemotherapy / methods*
Photosensitizing Agents / pharmacology
Protoporphyrins / metabolism
Siderophores / pharmacology
|
| IF |
0.642
|
| Times Cited |
13
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| Resource |
| Human and Animal Cells |
|
