A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production

  • Authors:
    • Chen‑Chen Ji
    • Yi‑Yang Hu
    • Guang Cheng
    • Liang Liang
    • Bo Gao
    • Ying‑Peng Ren
    • Jin‑Tao Liu
    • Xiu‑Li Cao
    • Min‑Hua Zheng
    • San‑Zhong Li
    • Feng Wan
    • Hua Han
    • Zhou Fei
  • View Affiliations

  • Published online on: December 13, 2019     https://doi.org/10.3892/ijo.2019.4942
  • Pages: 606-617
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem‑like cells (GSCs), by culturing patient‑derived primary GSCs as well as a GSC cell line in glucose‑restricted, β‑hydroxybutyrate‑containing medium (BHB‑Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB‑Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self‑renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB‑Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB‑Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia‑inducible factor 1 and B‑cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB‑Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.
View Figures
View References

Related Articles

Journal Cover

February-2020
Volume 56 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ji CC, Hu YY, Cheng G, Liang L, Gao B, Ren YP, Liu JT, Cao XL, Zheng MH, Li SZ, Li SZ, et al: A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production. Int J Oncol 56: 606-617, 2020.
APA
Ji, C., Hu, Y., Cheng, G., Liang, L., Gao, B., Ren, Y. ... Fei, Z. (2020). A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production. International Journal of Oncology, 56, 606-617. https://doi.org/10.3892/ijo.2019.4942
MLA
Ji, C., Hu, Y., Cheng, G., Liang, L., Gao, B., Ren, Y., Liu, J., Cao, X., Zheng, M., Li, S., Wan, F., Han, H., Fei, Z."A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production". International Journal of Oncology 56.2 (2020): 606-617.
Chicago
Ji, C., Hu, Y., Cheng, G., Liang, L., Gao, B., Ren, Y., Liu, J., Cao, X., Zheng, M., Li, S., Wan, F., Han, H., Fei, Z."A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production". International Journal of Oncology 56, no. 2 (2020): 606-617. https://doi.org/10.3892/ijo.2019.4942