Targeting the pentose phosphate pathway increases reactive oxygen species and induces apoptosis in thyroid cancer cells.
6-Aminonicotinamide
/ pharmacology
Cell Line, Tumor
Cell Survival
/ drug effects
Endoplasmic Reticulum Stress
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Glucosephosphate Dehydrogenase
Humans
NADP
/ metabolism
Oxidative Stress
/ drug effects
Oxythiamine
/ pharmacology
Pentose Phosphate Pathway
/ drug effects
Reactive Oxygen Species
/ metabolism
Thyroid Neoplasms
/ drug therapy
Apoptosis
Pentose phosphate pathway
Reactive oxygen species
Thyroid cancer
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
28
04
2019
revised:
24
09
2019
accepted:
24
09
2019
pubmed:
30
9
2019
medline:
21
10
2020
entrez:
30
9
2019
Statut:
ppublish
Résumé
The pentose phosphate pathway (PPP) plays an important role in the biosynthesis of ribonucleotide precursor and NADPH. Cancer cells frequently increase the flux of glucose into the PPP to support the anabolic demands and regulate oxidative stress. Consistently, metabolomic analyses indicate an upregulation of the PPP in thyroid cancer. In the present study, we found that the combination of glucose-6-phosphate dehydrogenase (G6PD) and transketolase inhibitors (6-aminonicotinamide and oxythiamine) exerted an additive or synergistic effect on cell growth inhibition in thyroid cancer cells. Targeting PPP significantly increased cellular reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress and apoptosis. Suppressed cell viability could be partially rescued with treatment with the ROS scavenger or apoptosis inhibitor but not ER-stress inhibitor. Taken together, dual PPP blockade leads to pharmacologic additivity or synergism and causes ROS-mediated apoptosis in thyroid cancer cells.
Identifiants
pubmed: 31563469
pii: S0303-7207(19)30297-7
doi: 10.1016/j.mce.2019.110595
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Oxythiamine
136-16-3
6-Aminonicotinamide
329-89-5
NADP
53-59-8
Glucosephosphate Dehydrogenase
EC 1.1.1.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110595Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.