| RRC ID |
61343
|
| 著者 |
Shibuya N, Inoue K, Tanaka G, Akimoto K, Kubota K.
|
| タイトル |
Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas.
|
| ジャーナル |
Oncology
|
| Abstract |
Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 μM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP(+) ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs.
|
| 巻・号 |
88(5)
|
| ページ |
309-19
|
| 公開日 |
2015-1-1
|
| DOI |
10.1159/000369905
|
| PII |
000369905
|
| PMID |
25591719
|
| MeSH |
Administration, Oral
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology*
Benzoxazoles / administration & dosage
Benzoxazoles / pharmacology*
Blotting, Western
Cell Line, Tumor
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / enzymology
Colorectal Neoplasms / metabolism*
Female
Glucose / metabolism
Glutathione Disulfide / metabolism
Glycolysis / drug effects
Humans
Japan
Lactic Acid / metabolism
Mice
Mice, Nude
Pentose Phosphate Pathway / drug effects*
Plant Extracts / administration & dosage
Plant Extracts / pharmacology*
Pyrimidines / administration & dosage
Pyrimidines / pharmacology*
Receptors, Peptide / metabolism
Resveratrol
Stilbenes / administration & dosage
Stilbenes / pharmacology*
TOR Serine-Threonine Kinases / antagonists & inhibitors*
Transplantation, Heterologous
Treatment Outcome
|
| IF |
2.642
|
| リソース情報 |
| ヒト・動物細胞 |
CACO-2(RCB0988) |
