The effect of thiamine supplementation on tumour proliferation

作者：Begoña Comı́n-Anduix, Joan Boren, S. Soler Martinez, C. García Moro, Josep J. Centelles, R V Trebukhina, N. E. Petushok, Wai‐Nang Paul Lee, László G. Boros, Marta Cascante · 发表于：European Journal of Biochemistry · 年份：2001 · DOI：10.1046/j.1432-1327.2001.02329.x · 被引用次数：181 · 研究领域：Alcoholism and Thiamine Deficiency、Cancer, Hypoxia, and Metabolism

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted ...