Thiamine supplementation to cancer patients: a double edged sword.
The objectives of this review are to (a) explain the mechanism by which thiamine (vitamin B1) promotes nucleic acid ribose synthesis and tumor cell proliferation via the nonoxidative transketolase (TK) pathway; (b) estimate the thiamine intake of cancer patients and (c) provide background information and to develop guidelines for alternative treatments with antithiamine transketolase inhibitors in the clinical setting. Clinical and experimental data demonstrate increased thiamine utilization of human tumors and its interference with experimental chemotherapy. Analysis of RNA ribose indicates that glucose carbons contribute to over 90% of ribose synthesis in cultured cervix und pancreatic carcinoma cells and that ribose is synthesized primarily through the thiamine dependent TK pathway (> 70%). Antithiamine compounds significantly inhibit nucleic acid synthesis and tumor cell proliferation in vitro and in vivo in several tumor models. The medical literature reveals little information regarding the role of the thiamine dependent TK reaction in tumor cell ribose production which is a central process in de novo nucleic acid synthesis and the salvage pathways for purines. Consequently, current thiamine administration protocols oversupply thiamine by 200% to 20,000% of the recommended dietary allowance, because it is considered harmless and needed by cancer patients. The thiamine dependent TK pathway is the central avenue which supplies ribose phosphate for nucleic acids in tumors and excessive thiamine supplementation maybe responsible for failed therapeutic attempts to terminate cancer cell proliferation. Limited administration of thiamine and concomitant treatment with transketolase inhibitors is a more rational approach to treat cancer.
Boros
L G
LG
Ohio State University College of Medicine, Department of Surgery, Columbus 43210, USA. Iboros@magnus.acs.ohio-state.edu
Brandes
J L
JL
Lee
W N
WN
Cascante
M
M
Puigjaner
J
J
Revesz
E
E
Bray
T M
TM
Schirmer
W J
WJ
Melvin
W S
WS
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002455:Cell Division; D017408:Guidelines as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009696:Nucleic Acids / Q000096:biosynthesis; D013831:Thiamine / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use*; D014174:Transketolase / Q000378:metabolism
D000970:Antineoplastic Agents; D009696:Nucleic Acids; D014174:Transketolase; D013831:Thiamine