Open Access

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

  • Authors:
    • Sheng Li
    • Chao Sun
    • Yu Gu
    • Xing Gao
    • Yuanlin Zhao
    • Yuan Yuan
    • Feng Zhang
    • Peizhen Hu
    • Weihua Liang
    • Kaiyu Cao
    • Jin Zhang
    • Zhe Wang
    • Jing Ye
  • View Affiliations

  • Published online on: January 28, 2019     https://doi.org/10.3892/mmr.2019.9903
  • Pages: 2509-2518
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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April-2019
Volume 19 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li S, Sun C, Gu Y, Gao X, Zhao Y, Yuan Y, Zhang F, Hu P, Liang W, Cao K, Cao K, et al: Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain. Mol Med Rep 19: 2509-2518, 2019
APA
Li, S., Sun, C., Gu, Y., Gao, X., Zhao, Y., Yuan, Y. ... Ye, J. (2019). Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain. Molecular Medicine Reports, 19, 2509-2518. https://doi.org/10.3892/mmr.2019.9903
MLA
Li, S., Sun, C., Gu, Y., Gao, X., Zhao, Y., Yuan, Y., Zhang, F., Hu, P., Liang, W., Cao, K., Zhang, J., Wang, Z., Ye, J."Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain". Molecular Medicine Reports 19.4 (2019): 2509-2518.
Chicago
Li, S., Sun, C., Gu, Y., Gao, X., Zhao, Y., Yuan, Y., Zhang, F., Hu, P., Liang, W., Cao, K., Zhang, J., Wang, Z., Ye, J."Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain". Molecular Medicine Reports 19, no. 4 (2019): 2509-2518. https://doi.org/10.3892/mmr.2019.9903