Carcinogenesis Advance Access originally published online on July 5, 2007
Carcinogenesis 2007 28(11):2291-2297; doi:10.1093/carcin/bgm149
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Folate receptor and human reduced folate carrier expression in HepG2 cell line exposed to fumonisin B1 and folate deficiency
1 Laboratory of Nutritional Genomics, Institut Polytechnique LaSalle Beauvais—Agrohealth EGEAL, 19 rue Pierre Waguet, F-60026 Beauvais cedex, France
2 INSERM U724, Cellular and Molecular Pathology in Nutrition, Vandoeuvre-les-Nancy, 54505 France
* To whom correspondence should be addressed. Tel: + 33 3 4406 38 67 Fax: +33 3 44 06 25 26; Email: abalo.chango{at}lasalle-beauvais.fr
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 its apoptotic effect is influenced by folate. Incubation of HepG2 cells with FB1 induced apoptosis in concentration and time-dependent manner in complete medium (experimental control medium, ECM), as well as in folate-depleted medium (FDM). FDM increased the toxicity of FB1 as the cells developed apoptosis within 24 h at 1 µM of FB1 instead of 100 µM in ECM. Whereas 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. FDM alone reduced FR protein expression by 12 ± 2% and 43 ± 1% at 48 and 72 h, respectively. The 5-methytetrahydrofolate attenuates apoptosis in a greater extent than the folic acid. However, its effects in preventing decrease of both folate transporters have not been observed. In conclusion, this study shows that the changes in the expression of FR 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.
Abbreviations: CB, cell buffer; ECM, experimental control medium; FB1, Fumonisin B1; FDM, folate-depleted medium; FR, folate receptor; GPI, glycosylphosphatidylinositol; MEM, Minimum Essential Medium Eagle's; MSM, MTHF-supplemented medium
Received March 9, 2007; revised May 25, 2007; accepted June 22, 2007.