Abstract Title:

Thiamine supplementation attenuated hepatocellular carcinoma in the Atp7b mouse model of Wilson's disease.

Abstract Source:

Anticancer Res. 2011 Oct ;31(10):3395-9. PMID: 21965752

Abstract Author(s):

Christian T Sheline

Article Affiliation:

Department of Ophthalmology and the Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, U.S.A. [email protected]


BACKGROUND: Wilson's disease is caused by a genetic defect in P-type Cu(2+)-ATPase (Atp7b), resulting in Cu(2+) accumulation in the liver, toxicity, and hepatocellular carcinoma. Exposure of HepG2 cells, and livers of Atp7b mutant mice to toxic Cu(2+) resulted in oxidation, (KGDH) and (PDH) enzyme inhibition, and death that was attenuated by thiamine.

MATERIALS AND METHODS: The effect of oral thiamine supplementation (2%) on hepatocellular carcinoma induced by Cu(2+) accumulation in the livers of Atp7b animals at 4, 6, 9, 12, 16, and 21 months was demonstrated using gross morphology and multi-nucleate analysis.

RESULTS: By 16 months of age, untreated Atp7b animals became moribund, their livers were>180% the weight of controls and>75% of their liver was cancerous. At 16 months the livers of thiamine treated Atp7b mice were<130% the weight of controls and<30% cancerous, and at 21 months the mice were still active. However thiamine was ineffective in a subcutaneous xenograft model.

CONCLUSION: This study suggests that thiamine may constitute a prophylactic for Wilson's disease-induced hepatocellular carcinoma.

Study Type : Animal Study

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