Abstract
Curcumin and resveratrol were evaluated for their potential to cause reversal of promoter hypermethylation and associated gene expression of FANCF in SiHa cell line. Methylation specific PCR along with bisulphite sequencing revealed the demethylation of 12 CpG sites out of 15 CpG sites spanning +280 to +432 region of FANCF promoter after treatment with curcumin and fivefold up regulation of FANCF gene expression as shown by qRT-PCR. In vitro methylation assay also showed that M.SssI an analogue of DNMT1 was effectively inhibited at 50 μM concentration of curcumin. Resveratrol was not found to be effective in causing reversal of promoter hypermethylation of FANCF gene when used at 20 μM for 4 days in SiHa cell line.
Similar content being viewed by others
References
Teng I-W, Hou P-C, Lee K-D et al (2011) Targeted methylation of two tumor suppressor genes is sufficient to transform mesenchymal stem cells into cancer stem/initiating cells. Cancer Res 71(13):4653–4663
Wentzensen N, Sherman ME, Schiffman M et al (2009) Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol 112(2):293–299
Siddique MA, Nakanishi K, Taniguchi T et al (2001) Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. Exp Hematol 29:1448–1455
Léveillé F, Blom E, Medhurst AL et al (2004) The Fanconi Anemia gene product FANCF is a flexible adaptor protein. J Biol Chem 279(38):39421–39430
De Winter JP, Weel LV, De Groot J et al (2000) The Fancomi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet 9(18):2665–2674
Taniguchi T, Tischkowitz M, Ameziane N et al (2003) Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 9:568–574
Marsit CJ, Liu M, Nelson HH et al (2004) Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival. Oncogene 23:1000–1004
Narayan G, Arias-Pulido H, Koul S et al (2003) Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer 2:24
Narayan G, Arias-Pulido H, Nandula SV et al (2004) Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Cancer Res 64:2994–2997
Bakker S T, van de Vrugt HJ, Visser JA et al (2011) FANCF-deficient mice are prone to develop ovarian tumours. J Pathol. doi:10.1002/path.2992
Herman JG, Umar A, Polyak K et al (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95:6870–6875
Brueckner B, Boy RG, Siedlecki P et al (2005) Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 65:6305–6311
Soengas MS, Capodieci P, Polsky D et al (2001) Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409:207–211
Robert MF, Morin S, Beaulieu N et al (2003) DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 33:61–65
Siedlecki P, Boy RG, Musch T et al (2006) Discovery of two novel, small-molecule inhibitors of DNA methylation. J Med Chem 49:678–683
Fang MZ, Wang Y, Ai N et al (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563–7570
Wang Z, Chen H (2010) Genistein increases gene expression by demethylation of WNT5a promoter in colon cancer cell line SW1116. Anticancer Res 30:4537–4546
Liu Z, Liu S, Xie Z et al (2009) Modulation of DNA methylation by a sesquiterpene lactone parthenolide. J Pharmacol Exp Ther 329(2):505–514
Morey Kinney SR, Zhang W, Pascual M et al (2009) Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate. Cancer Prev Res 2:1065–1075
Jha AK, Nikbakht M, Parashar G et al (2010) Reversal of hypermethylation and reactivation of the RARβ2 gene by natural compounds in cervical cancer cell lines. Folia Biologica (Praha) 56:195–200
Liu ZF, Xie ZL, Jones W et al (2009) Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett 19:706–709
Liu YL, Yang HP, Gong L et al (2011) Hypomethylation effects of curcumin, demethoxycurcumin and bisdemethoxycurcumin on WIF-1 promoter in non-small cell lung cancer cell lines. Mol Med Report 4(4):675–679
Medina-Franco JL, Lopez-Vallejo F, Kuck D et al (2011) Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach. Mol Divers 15(2):293–304
Heckenkamp J, Leszczynski D, Schiereck J et al (1999) Different effects of photodynamic therapy and gamma irradiation on vascular smooth muscle cells and matrix: implications for inhibiting restenosis. Arterioscler Thomb Vasc Biol 19:2154–2161
Tokunaga E, Okada S, Kitao H, Shiotani S et al (2011) Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer. Breast Cancer 18(2):120–123
Khor TO, Huang Y, Wu Tien-Yuan et al (2011) Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol 82:1073–1078
Yoo J, Medina-Franco JL (2011) Homology modeling, docking and structure-based pharmacophore of inhibitors of DNA methyltransferase. J Comput Aided Mol Des 25(6):555–567
Acknowledgments
This study was supported by Council of Scientific and Industrial Research (CSIR), New Delhi, India.
Conflict of interest
The authors declare that there are no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parashar, G., Parashar, N.C. & Capalash, N. Curcumin causes promoter hypomethylation and increased expression of FANCF gene in SiHa cell line. Mol Cell Biochem 365, 29–35 (2012). https://doi.org/10.1007/s11010-012-1240-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-012-1240-z