Work

αKG-induced oxidative stress and mTOR inhibition as a therapeutic strategy for liver cancer

Year: 2025

Type: article

Abstract: Despite the availability of targeted therapies, liver cancer remains a severe health burden. The need for adjuvant therapy to improve treatment efficacy and prevent recurrence is emerging. Alpha-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle and a cofactor for various oxygenases. A critical role of this multifunctional metabolite has started to be revealed in physiological and pathological conditions. We found that αKG exerts various anti-tumor effects in liver cancer cells. Our kinetic transcriptome study suggested that increasing reactive oxygen species and inhibiting mTORC1 signaling underlies. Indeed, αKG treatment elevated oxidative stress and induced DNA damage, presumably caused by early downregulation of the antioxidant gene SLC7A11. Further, we validated impaired mTOR signaling and decreased cellular energy production. This unique mechanism underscores αKG's potential as a liver cancer therapy by harnessing oxidative stress and disrupting metabolic signaling. These findings could provide valuable insights into further exploration of αKG as a promising therapeutic agent in liver cancer.

Source: Medical Oncology

DOI: 10.1007/s12032-025-02653-0

Authors: Sung Kyung Choi, Myoung Jun Kim, Jueng Soo You

Institution: Konkuk University

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,290