Vitamin D Receptor (VDR) polymorphism and antiproliferative activity of cholecalciferol in cancer cells

Authors

DOI:

https://doi.org/10.33448/rsd-v9i12.10810

Keywords:

Breast Cancer; Glioblastoma; Vitamin D receptor; PCR-RFLP; SNP; Brain cancer.

Abstract

Vitamin D (VD) is a steroid hormone with multiple biological functions in the body and its activity requires the binding to the receptor named VDR. VDR polymorphisms seems to be involved in the development of several types of cancer. Herein we performed the genotyping of two VDR polymorphisms (Fok I and Taq I) in MCF-7 breast cancer and U87-MG glioblastoma (GBM) cell lines and investigated the antiproliferative effect of the VD analog cholecalciferol. Polymorphisms were identified by PCR-RFLP and the effect of VD was determined by viability and clonogenic assays. VD inhibited the growth of both tumor cells in vitro. MCF-7 cells were more sensitive than U87-MG cells at concentrations ranging from 0.1nM to 1000nM. The same primer pairs used for PCR amplification of VDR gene in MCF-7 failed to amplify a fragment of expected size in the U87-MG cell line. VDR Fok I and Taq I polymorphisms in breast cancer MCF-7 cells were characterized as FF (CC) and TT respectively. The absence of amplification of VDR gene fragment in U87-MG suggests a possible chromosomal rearrangement and/or impairment of gene expression of VDR which could interfere in the sensitivity of this cell line to vitamin D.

References

Ahmed, H., Makonnen, E., Fotoohi, A., Yimer, G., Seifu, D., Assefa, M., et al. (2019). Vitamin D Status and Association of VDR Genetic Polymorphism to Risk of Breast Cancer in Ethiopia. Nutrients, 11, 2, 289. doi: 10.3390/nu11020289.

Alimirah, F., Peng, X., Murillo, G., Mehta, R. G. (2011). Functional Significance of Vitamin D Receptor FokI Polymorphism in Human Breast Cancer Cells, Plos one, e16024.

Anic, G. M. (2012). An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome. Cancer Causes Control, 23, 9, 1443–1449. doi: 10.1371/journal.pone.0016024.

Bao, B-Y.,Yeh, S-D., & Lee, Y-F. (2006). 1a,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulationof selective proteases (2006). Carcinogenesis, 27, 32–42. doi: 10.1093/carcin/bgi170.

Boneti, R. S., & Fagundes, R. B. Vitamin D and Cancer (2013). Revista da AMRIG, 57 (1):71-77. Retrieved from: https://revistapresenca.celsolisboa.edu.br/index.php/numer ohum/article/view/122.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin. 68 (6), 394–424. doi:10.3322/caac.21492.

Chen, W. Y., Berone-Johnson, E. R., Hunter, D. J., Willett, W. C., Hankinson, S. E. (2005). Association between polymorphism in the vitamin D receptor and breast cancer risk. Cancer Epidemiol Biomarkers Prev, 14, 2335–2339. doi: 10.1158/1055-9965.EPI-05-0283.

Chen, Y. (2018). Vitamin D receptor suppresses proliferation and metastasis in renal cell carcinoma cell lines via regulating the expression of the epithelial Ca2+ channel TRPV5. PLoS One, 13, e0195844. doi: 10.1371/journal.pone.0195844.

DeBerardinis, A. M., Lemieux, S., Hadden, M. K. Analogues of the Inhoffen-Lythgoe diol with antiproliferative activity (2013). Bioorg Med Chem Lett. 19, 5367-5370. doi: 10.1016/j.bmcl.2013.07.054.

Dolecek, T. A., et al., (2012). CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-oncology, 14 (suppl 5), v1-v49. doi: 10.1093/neuonc/nos218.

Evans, M. A., Kim, H. A., Ling, Y. H., Uong, S., Vinh, A., De Silva, T. M., et al. (2018). Vitamin D3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke. Neuro Molecular Med, 20 (1):147-159. doi: 10.1007/s12017-018-8484-z.

Ferronato, M. J., Alonso, E. N., Salomón, D. G., Fermento, M. E., Gandini, N. A., Quevedo, M. A., et al. (2018). Antitumoral effects of the alkynylphosphonate analogue of calcitriol EM1 on glioblastoma multiforme cells. J Steroid Biochem Mol Biol. 178, 22-35. doi: 10.1016/j.jsbmb.2017.10.019.

Franken, N. A. P., Rodermond, H. M., Stap, J., Haveman, J., & van Bree, C. Clonogenic assay of cells in vitro. Nature Protocols; 2006, 1 n 5, doi: 10.1038/nprot.2006.339. doi: 10.1038/nprot.2006.339.

Garland, C. F., Garland, F. C., Gorham, E. D., Lipkin, M., Newmark, H., Mohr, S. B., et al. (2006). The Role of Vitamin D in Cancer Prevention. American Journal of Public Health, 96 (2): 252–261. doi: 10.2105/AJPH.2004.045260

Giovannucci, E. (2005). The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control, 16 (2):83-95. doi: 10.1007/s10552-004-1661-

Gocek, E., & Studzinski, G. P. (2009). Vitamin D and differentiation in câncer. Crit Rev Clin Lab Sci., (4). doi:10.1080/10408360902982128.

Gross, C., Krishnan, A. V., Malloy, P. J., Eccleshall, T. R., Zhao, X. Y., Feldman, D. (1998). The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. J Bone Miner Res, 13 (11), 1691–1699. doi:10.1359/jbmr.1998.13.11.1691.

Grundmann, M., Haidar, M., Placzko, S., Niendorf, R., Darashchonak, N., Hubel, C. A., & Von Versen-Höynck, F. (2012). Vitamin D Improves the Angiogenic Properties of Endothelial Progenitor Cells. Am J Physiol Cell Physiol. 303 (9), C954–C962. doi: 10.1152/ajpcell.00030.2012.

Guy, M., Lowe, L. C., Bretherton-Watt, D., Mansi, J. L., Peckitt, C., et al. (2004). Vitamin D receptor gene polymorphisms and breast cancer risk. Clin Cancer Res, 10, 5472–5481. DOI: 10.1158/1078-0432.CCR-04-0206.

Hardiman, G., Savage, S. J., Hazard, E. S., Wilson, R. C., Courtney, S. M., Smith, M. T., et al. (2016) Systems analysis of the prostate transcriptome in African–American men compared with European–American men. Pharmacogenomics, 17(10), 1129–1143. doi: 10.2217/pgs-2016-0025.

Koh, C. M (2013). Isolation of Genomic DNA from Mammalian Cells. Methods in Enzymology, 529. doi: 10.1016/B978-0-12-418687-3.00013-6.

Lu, D., Jing, L., Zhang, S. (2016). Vitamin D Receptor Polymorphism and Breast Cancer Risk a Meta-Analysis (2016). Medicine, 95. doi: 0.1097/MD.0000000000003535.

McCullough, M. L., Stevens, V. L., Diver, W. R., Feigelson, H. S., Rodriguez, C., et al. (2007). Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Res, 9: R9. doi:10.1186/bcr1642.

Mousa, N., Helena, T., Robert, S., Barbora, C. (2018). Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Nutr Rer, 76, 380 – 394. doi: 0.1093/nutrit/nux077.

Nilufer, G., et al (2016). The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis. Renal Failure, 545–551. doi: 10.3109/0886022X.2016.1148557.

Pan, L., Matloob, A. F., Du, J., Pan, H., Dong, Z., Zhao, J., et al (2009). Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A ⁄sodium butyrate-induced and 5-aza-2¢-deoxycytidine-induced PTEN upregulation. FEBS Journal, 277, 989–999. doi:10.1111/j.1742-4658.2009.07542.x.

Rai, V., Abdo, J., Agrawal, S., & Agrawal, D. K. (2017). Vitamin D Receptor Polymorphism and Cancer: An Update. Anticancer research, 3991-4003, doi: 10.21873/anticanres.11784. doi: 10.21873/anticanres.11784.

Raza, S., Dhasmana, A., Bhatt, M. L. B., Lohani, M., Arif, J. M. (2019). Molecular Mechanism of Cancer Susceptibility Associated withFok1 Single Nucleotide Polymorphism of VDR in Relation to Breast Cancer. Asian Pac J Cancer Prev, 20, (1). doi:10.31557/APJCP.2019.20.1.199.

Salomon, D. G., Fermento, M. E., Gandini, N. A., Ferronato, M. J., Arevalo, J., et al. (2014). Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme. J Neuro oncol, 1, 49-60. doi: 10.1007/s11060-014-1416-3.

Saracligil, B., Ozturk, B., Unlu, A., Abusoglu, S., Tekin, G. (2017). The effect of vitamin D on MCF-7 breast cancer cell metabolism. Bratisl Med J, 118, 2 101 – 106.

Sinotte, M., Rousseau, F., Ayotte, P., Dewailly, E., Diorio, C., et al. (2008). Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population. Endocr Relat Cancer, 15, 975–983. doi: 10.4149/BLL_2017_021.

Strober, W. Trypan Blue Exclusion Test of Cell Viability (2015). Curr Protoc Immuno. 111: A3.B.1–A3.B.3. doi: 10.1002/0471142735.ima03bs111.

Toptaş, B., Kafadar, A. M., Cacina, C., Turan, S., Yurdum, L. M., Yiğitbaşı, N., et al. (2013). The vitamin D receptor (VDR) gene polymorphisms in Turkish brain cancer patients. Biomed Res Int, 295791. doi:10.1155/2013/2957

Vargas-Rondón, N., Villegas, V. E., & Rondón-Lagos, M. (2018). The Role of Chromosomal Instability in Cancer and Therapeutic Responses. Cancers, 10, 4. doi: 10.3390/c ancers10010004.

Wang, Y., Zhu, J., DeLuca, H. F. (2012). Where is the vitamin D receptor? Arch Biochem Biophys, 523 (1):123–133. doi:10.1016/j.abb.2012.04.001.

Yaylım-Eraltan, I., Arzu Ergen, H., Arıkan, S., Okay, E., Ozturk, O., & Bayrak, S. (2007). Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer. Cell Biochem Funct, 731-737. doi: 10.1002/cbf.1386.

Yuan, L., Jiang, R., Yang, Y., Ding, S., & Deng, H. (2012). 1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and down regulates cytochrome P4501B1through the COX-2/PGE2 pathway. Oncology reports, 2131-2137. doi: 10.3892/or.2012.2031.

Zerwekh, E. J. (2008) Blood biomarkers of vitamin D status. Am J Clin Nutr, 87 (4), 1087S-91S. doi:10.1093/ajcn/87.4.108.

Zheng, W., Tayyari, F., Gowda, G. A., Raftery, D., McLamore, E. S., Shi, J., et al. (2013). 1, 25 Dihydroxyvitamin D Regulation of Glucose Metabolism in Harvey-ras Transformed MCF10A Human Breast Epithelial Cells. J Steroid Biochem Mol Biol, 2013138, 81–89. doi: 10.1016/j.jsbmb.2013.03.012.

Zou, J., Landy, H., Feun, L., Xu, R., Lampidis, T., Wu, C. J., et al. (2000). Correlation of a unique 220-kDa protein with vitamin D sensitivity in glioma cells Biochemical Pharmacology, 60(9). doi: 10.1016/S0006-2952(00)00438-X.

Downloads

Published

14/12/2020

How to Cite

LOPES, A. R.; FELIPE, V. G.; SANTOS, R. G. dos; SANTOS, W. G. dos. Vitamin D Receptor (VDR) polymorphism and antiproliferative activity of cholecalciferol in cancer cells. Research, Society and Development, [S. l.], v. 9, n. 12, p. e8991210810, 2020. DOI: 10.33448/rsd-v9i12.10810. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/10810. Acesso em: 24 apr. 2024.

Issue

Section

Health Sciences