Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain

Increasing evidence has indicated that mutations of isocitrate dehydrogenase 1/2 (IDH1/2) contribute to the metabolic reprogramming of cancer cells; however their functions in lipid metabolism remain unknown. In the present study, the parental and IDH1 (R132H/+) mutant HCT116 cells were treated with various concentrations of oleic acid (OA) or palmitic acid (PA) in the presence or absence of glucose. The results demonstrated that mutation of IDH1 exacerbated the effects of OA and PA on cell viability and apoptosis, and consistently elevated the production of reactive oxygen species in HCT116 cells, particularly in the absence of glucose. Furthermore, mutation of IDH1 inhibited the rate of fatty acid oxidation (FAO), but elevated the glucose consumption in HCT116 cells. The results of immunoblotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) indicated that the expression of glucose transporter 1 was upregulated, whereas that of carnitine palmitoyl transferase 1 was downregulated in IDH1 mutant HCT116 cells. Although mitochondrial DNA quantification demonstrated that mutation of IDH1 had no effect on the quantity of mitochondria, immunoblotting and RT‑qPCR revealed that mutation of IDH1 in HCT116 cells significantly downregulated the expression of cytochrome c (CYCS) and CYCS oxidase IV, two important components in mitochondrial respiratory chain. These results indicated that mutation of IDH1 aggravated the fatty acid‑induced oxidative stress in HCT116 cells, by suppressing FAO and disrupting the mitochondrial respiratory chain. The results of the present study may provide novel insight into therapeutic strategies for the treatment of cancer types with IDH mutation.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Molecular medicine reports - 19(2019), 4 vom: 19. Apr., Seite 2509-2518

Sprache:

Englisch

Beteiligte Personen:

Li, Sheng [VerfasserIn]
Sun, Chao [VerfasserIn]
Gu, Yu [VerfasserIn]
Gao, Xing [VerfasserIn]
Zhao, Yuanlin [VerfasserIn]
Yuan, Yuan [VerfasserIn]
Zhang, Feng [VerfasserIn]
Hu, Peizhen [VerfasserIn]
Liang, Weihua [VerfasserIn]
Cao, Kaiyu [VerfasserIn]
Zhang, Jin [VerfasserIn]
Wang, Zhe [VerfasserIn]
Ye, Jing [VerfasserIn]

Links:

Volltext

Themen:

EC 1.1.1.41
EC 1.1.1.42.
Fatty Acids
Glucose
IDH1 protein, human
IY9XDZ35W2
Isocitrate Dehydrogenase
Journal Article

Anmerkungen:

Date Completed 01.08.2019

Date Revised 09.03.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.3892/mmr.2019.9903

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM293467889