| RRC ID |
44815
|
| 著者 |
Sugiyama Y, Hagiya Y, Nakajima M, Ishizuka M, Tanaka T, Ogura S.
|
| タイトル |
The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis.
|
| ジャーナル |
Oncol Rep
|
| Abstract |
Our previous study demonstrated that 5-aminolevulinic acid (ALA) administered to mice stimulates oxidative phosphorylation by upregulation of the mitochondrial respiratory chain complex IV enzyme cytochrome c oxidase (COX). The present study investigated whether ALA disrupts the Warburg effect, which represents a shift in ATP generation from oxidative phosphorylation to glycolysis, protecting tumor cells against oxidative stress-mediated apoptosis. The human lung carcinoma cell line A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption. Furthermore, ALA suppressed glycolysis-mediated acidosis. This normalization of the ATP metabolic pathways significantly increased the generation of superoxide anion radical (O2•-) and the functional expression of active caspase-3, leading to caspase-dependent apoptosis. These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death. Use of this endogenous compound might constitute a novel approach to cancer therapy.
|
| 巻・号 |
31(3)
|
| ページ |
1282-6
|
| 公開日 |
2014-3-1
|
| DOI |
10.3892/or.2013.2945
|
| PMID |
24366173
|
| MeSH |
Aminolevulinic Acid / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Caspase 3 / metabolism*
Cell Line, Tumor
Cell Survival / drug effects
Drug Screening Assays, Antitumor
Glycolysis / drug effects*
Humans
Hydrogen-Ion Concentration
Oxidative Phosphorylation / drug effects
Superoxides / metabolism
|
| IF |
3.417
|
| 引用数 |
8
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
A549 |
