Carcinogenesis Advance Access published online on July 5, 2007
Carcinogenesis, doi:10.1093/carcin/bgm149
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Folate receptor and human reduced folate carrier expression in HepG2 cell line exposed to fumonisin B1 and folate deficiency
1 Institut Polytechnique LaSalle Beauvais - Agrohealth EGEA, Beauvais, France
2 INSERM U724, Cellular and Molecular Pathology in Nutrition, Vandoeuvre-les-Nancy
* Corresponding author, mailing address: Laboratory of Nutritional Genomics, Institut Polytechnique LaSalle de Beauvais, 19, rue Pierre Waguet, F-60026 Beauvais cedex, France., E-mail: abalo.chango{at}lasalle-beauvais.fr., Fax: + 33 3 44 06 25 26.
Fumonisin B1 (FB1) induces apoptosis and decreases the cellular uptake of 5-methyltetrahydrofolate. Two folate-transporters (Folate Receptor, FR and Reduced Folate Carrier, hRFC1), are involved in the cell uptake of folate. We aimed to study whether FB1 modifies the expression of the FR and the hRFC1 and whether it apoptotic effect is influenced by folate. Incubation of HepG2 cells with FB1 induced apoptosis in concentration and time dependent manner in complete medium (ECM), as well as in folate depleted medium (FDM). FDM increased the toxicity of FB1 as the cells developed apoptosis within 24h at 1µM of FB1 instead of 100µM in ECM. While FR protein expression in cells grown in ECM was significantly inhibited after apoptosis event, protein expression of the hRFC1 was rather increased. The hrfc1 transcription was decreased in the treated cells. Under folate deficient conditions, dramatic changes were observed on both transcriptional and post-transcriptional expression of the two transporters. Folate-depleted medium alone reduced FR protein expression by 12±2% and 43±1% at 48 and 72h, respectively. The 5-methytetrahydrofolate attenuates apoptosis in a greater extent than the folic acid. However its effects in preventing decrease of both folate transporters has not been observed. In conclusion, this study shows that the changes in the expression of folate receptor after FB1 addition are probably a consequence of the FB1 toxicity. The response to FB1 by HepG2 cell lines is influenced by folate status and by folate form. 5-methyltetrahydrofolate appears to be more effective in preventing apoptosis than folic acid.
Key Words: Apoptosis folate-transporter fumonisin methyltetrahydrofolate reduced folate carrier
Received March 9, 2007; revised May 25, 2007; accepted June 22, 2007.