RRC ID 61343
Author Shibuya N, Inoue K, Tanaka G, Akimoto K, Kubota K.
Title Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas.
Journal 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.
Volume 88(5)
Pages 309-19
Published 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
Human and Animal Cells CACO-2(RCB0988)