Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy.

Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Research Abstract Details 

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Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Abstract Text:

Tumor cells have an enhanced requirement for glucose, amino acids and DNA precursors. Since folates are required for the synthesis of thymidine and purines, the metabolism of folate has been exploited as an anti-cancer target for over 6 decades, with emphasis on the inhibition of DNA synthesis. However, folate is also used to generate methionine, which is essential for proliferation by virtue of its role in protein synthesis, polyamine synthesis and transmethylation reactions. Tumor-derived cell lines and human tumor xenografts have been shown to be methionine dependent i.e., they are unable to survive without methionine and are unable to efficiently utilize homocysteine, the immediate metabolic precursor of methionine. Since non-transformed cells are methionine-independent, the targeting of methionine metabolism presents an opportunity to selectively disrupt the unique metabolic networks in cancer cells. This chapter provides an overview of the critical role of folate and methionine metabolism in tumor cells and summarizes the current anti-folate and anti-methionine strategies to inhibit growth of transformed lines and tumors. We also present our work on the development of a novel anti-cancer target, methylenetetrahydrofolate reductase (MTHFR), a key enzyme of both folate and methionine metabolism. Our data demonstrate that antisense-mediated inhibition of MTHFR is associated with increased cytotoxicity in vitro and with decreased growth of tumors in vivo. These findings warrant further investigation of this enzyme and the methionine biosynthetic pathway in exploring new strategies for cancer chemotherapy.

Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Publishing Authors By Initials

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Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Journal Published:

PUBLICATION TYPE: Review

Journal: Current pharmaceutical design

VOLUME: 14

Page Numbers: 1143-50

Journal Abbreviation: Curr. Pharm. Des.

ISSN: 1873-4286

DAY: 23

MONTH: 06

YEAR: 2008

Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Information

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LANGUAGE: eng

NlmUniqueID: 9602487

Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Keywords Mesh Terms:

KEYWORDS: Oligonucleotides, Antisense

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy. Information

Substance Name: Methylenetetrahydrofolate Reductase (NAD

Registry Number: EC 1.5.1.20

Grant and Affiliation Information for Methylenetetrahydrofolate reductase (MTHFR): a novel target for cancer therapy.

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Country: Netherlands

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MEDLINETA: Curr Pharm Des

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