E. Muto-Fujita, B. Yamaoka, N. Abe, K. Fujiwara and S. Uehara (2025). Ketone Bodies Inhibit Growth of Hepatoblastoma and Rhabdoid Tumor of the Kidney Cells. Anticancer research, 45(7), 3089-3097. https://doi.org/10.21873/anticanres.17673

PubMed 40578956

[Abstract]
BACKGROUND/AIM: The prognosis for high-risk pediatric cancers remains poor, necessitating the development of novel therapies. The ketogenic diet (KD) has shown efficacy in various adult cancers; however, its impact on pediatric solid tumors remains underexplored. This study investigated the impact of ketone bodies (KBs) on hepatoblastoma and rhabdoid tumor of the kidney.

MATERIALS AND METHODS: Human hepatoblastoma cell line (Huh6), human rhabdoid tumors of the kidney cell lines (G401, WT-CLS1), and human foreskin derived fibroblast cell line (HFF) were used in this study. Cells were cultured in control media, glucose-free media, and glucose-free media supplemented with acetoacetate or β-hydroxybutyrate. Cell viability was assessed using the WST-8 assay. Intracellular ATP concentrations and the expression of KBs-metabolizing enzymes, Succinyl-CoA: 3-oxoacid CoA transferase (SCOT) and 3-hydroxybutyrate dehydrogenase-1 (BDH1), were evaluated using an ATP assay and qRT-PCR, respectively.

RESULTS: The WST-8 assay demonstrated Huh6, G401, and WT-CLS1 growth inhibition in glucose-free media, which was not rescued by KBs-supplemented media. The ATP assay showed decreased intracellular ATP levels in Huh6 and G401 but not in WT-CLS1. Expression levels of SCOT and BDH1 in Huh6, G401, and WT-CLS1 cells were significantly lower than those in HFF cells.

CONCLUSION: The growth of Huh6, G401, and WT-CLS1 cells was inhibited under glucose-free conditions and not rescued by KBs. The current results strongly suggest that KD is a highly promising treatment for patients with hepatoblastoma and rhabdoid tumor of the kidney.