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The Effect of Folic Acid Supplementation on Chemosensitivity to 5-fluorouracil in a Xenograft Model of Human Colon Carcinoma

Folate blood levels in North America have dramatically increased over the past decade owing to folic acid (FA) fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer (CRC) patients use vitamin supplements containing FA while receiving chemotherapy whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of human colon cancer cells to 5FU, the cornerstone of CRC treatment, using a xenograft model. FA supplementation was associated with a non-dose dependent decrease in chemosensitivity, where mice receiving 8 mg FA did not respond to 5FU and had greater tumor growth with treatment, compared to 2 (control) or 25 mg FA. Results of this study pose concern given the drastically increased intake of FA, particularly among recently diagnosed CRC patients, and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate underlying mechanisms.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33249
Date20 November 2012
CreatorsIshiguro, Lisa
ContributorsKim, Young-In
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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