Putative Role of Fatty Acid Metabolic Therapy Using Ketogenic Diet and HIF-1α Inhibition in Hepatocellular Carcinoma: Evidence from an In Vitro Study.

ABSTRACT: Hypoxia-inducible factor-1 (HIF-1) enhances cancer cell survival in hypoxic conditions. The ketogenic diet (KGD), characterized by low-carbohydrate and high-fat intake, has been widely used for epilepsy treatment and reported to have antitumor potential. However, its impact on hypoxic cancer cells remains poorly understood. This study examined the effects of combining the HIF-1α inhibitor YC-1 with the KD formula KetoCal^® on hypoxic hepatocellular carcinoma (HCC) cells. In vitro, HIF-1α knockdown (KD) and scramble control (SC) Hep3B and HepG2 cells were treated with palmitic acid (PA) and/or β-hydroxybutyrate (BOH) to mimic the KGD environment. PA significantly induced cell death and reactive oxygen species (ROS) in hypoxic KD cells, and this effect was further enhanced by BOH.

SUBMITTER: Kimura N 

PROVIDER: S-EPMC12732810 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature