The Role of Vitamin D in Preventing Colorectal Carcinogenesis: A Review of Molecular Mechanisms

The Role of Vitamin D in Preventing Colorectal Carcinogenesis

A Review of Molecular Mechanisms

Authors

  • Fauzan Herdian Indonesian Radiation Oncology Society
  • Fahmi Radityamurti Indonesian Radiation Oncology Society
  • Tiara Bunga Mayang Permata Indonesian Radiation Oncology Society
  • Handoko Indonesian Radiation Oncology Society
  • Henry Kodrat Indonesian Radiation Oncology Society
  • Endang Nuryadi Indonesian Radiation Oncology Society
  • Heri Wibowo Universitas Indonesia Faculty of Medicine
  • Soehartati Gondhowiardjo Indonesian Radiation Oncology Society

DOI:

https://doi.org/10.29169/1927-5951.2021.11.15

Keywords:

Carcinogenesis, Review, Colorectal Cancer, Vitamin D

Abstract

Introduction: Colorectal carcinoma is one of the cancers with a high disease burden globally. Previous observational studies have found a connection between colorectal cancer incidence with sunlight exposure and vitamin D levels. Subsequent studies investigated this relationship further and found various anti-tumoral pathways regulated by vitamin D in colorectal tissue. This paper aims to elucidate the actions of those pathways in preventing the malignant transformation of the colorectal cell by reviewing relevant literature.

Methods: A search was conducted on several medical literature electronic databases for original research studying the effects of vitamin D treatment on colorectal adenoma and colorectal cancer and its underlying anti-tumoral mechanism. A total of 122 studies were included for evaluation.

Results: Twenty-seven studies passed for analysis. These in vitro and in vivo study reveals that vitamin D treatment can suppress cell proliferation, induce apoptosis, maintain cellular differentiation, reduce the pro-inflammatory response, inhibit angiogenesis, and hinder metastatic progression in colorectal cancer and colorectal adenoma cells by regulating associated gene transcription or directly prevents activation of selected signalling pathways. Five studies have also shown that adding calcium to vitamin D treatment increases the anti-tumoral activity of vitamin D through cross-talk between both of their pathways.

Conclusion: Vitamin D could potentially impede colorectal cancer transformation and growth through interaction with various signalling pathways and regulating gene transcription. Further clinical studies are needed to confirm whether vitamin D can be used as the basis of targeted colorectal cancer therapy using its inherent anti-tumoral properties.

Author Biographies

Fauzan Herdian, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Fahmi Radityamurti, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Tiara Bunga Mayang Permata, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Handoko, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Henry Kodrat, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Endang Nuryadi, Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

Heri Wibowo, Universitas Indonesia Faculty of Medicine

Laboratorium Terpadu, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Soehartati Gondhowiardjo , Indonesian Radiation Oncology Society

Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.

https://doi.org/10.3322/caac.21492 DOI: https://doi.org/10.3322/caac.21492

Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Gastroenterology Rev 2019; 14: 89-103.

https://doi.org/10.5114/pg.2018.81072 DOI: https://doi.org/10.5114/pg.2018.81072

Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006; 92: 4-8.

https://doi.org/10.1016/j.pbiomolbio.2006.02.016 DOI: https://doi.org/10.1016/j.pbiomolbio.2006.02.016

Nagpal S, Na S, Rathnachalam R. Noncalcemic Actions of Vitamin D Receptor Ligands. Endocrine Reviews 2005; 26: 662-87.

https://doi.org/10.1210/er.2004-0002 DOI: https://doi.org/10.1210/er.2004-0002

Garland CF, Garland FC. Do Sunlight and Vitamin D Reduce the Likelihood of Colon Cancer? Int J Epidemiol 1980; 9: 227-31.

https://doi.org/10.1093/ije/9.3.227 DOI: https://doi.org/10.1093/ije/9.3.227

Garland CF, Garland FC, Shaw EK, Comstock GW, Helsing KJ, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: Eight-year prospective study. Lancet 1989; 334: 1176-8.

https://doi.org/10.1016/S0140-6736(89)91789-3 DOI: https://doi.org/10.1016/S0140-6736(89)91789-3

Wali RK, Khare S, Tretiakova M, Cohen G, Nguyen L, Hart J, et al. Ursodeoxycholic Acid and F6-D3 Inhibit Aberrant Crypt Proliferation in the Rat Azoxymethane Model of Colon Cancer: Roles of Cyclin D1 and E-Cadherin. Cancer Epidemiol Biomarkers Prev 2002; 11: 1653-62.

Yang K, Lamprecht SA, Shinozaki H, Fan K, Yang W, Newmark HL, et al. Dietary Calcium and Cholecalciferol Modulate Cyclin D1 Expression, Apoptosis, and Tumorigenesis in Intestine of adenomatous polyposis coli1638N/+ Mice. J Nutr 2008; 138: 1658-63.

https://doi.org/10.1093/jn/138.9.1658 DOI: https://doi.org/10.1093/jn/138.9.1658

Maier S, Daroqui MC, Scherer S, Roepcke S, Velcich A, Shenoy SM, et al. Butyrate and vitamin D3 induce transcriptional attenuation at the cyclin D1 locus in colonic carcinoma cells. J Cell Physiol 2009; 218: 638-42.

https://doi.org/10.1002/jcp.21642 DOI: https://doi.org/10.1002/jcp.21642

Aggarwal A, Höbaus J, Tennakoon S, Prinz-Wohlgenannt M, Graça J, Price SA, et al. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor. J Steroid Biochem Mol Biol 2016; 155: 231-8.

https://doi.org/10.1016/j.jsbmb.2015.02.006 DOI: https://doi.org/10.1016/j.jsbmb.2015.02.006

Evans SR, Soldatenkov V, Shchepotin EB, Bogrash E, Shchepotin IB. Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis. Int J Oncol 1999.

https://doi.org/10.3892/ijo.14.5.979 DOI: https://doi.org/10.3892/ijo.14.5.979

Wilson AJ, Velcich A, Arango D, Kurland AR, Shenoy SM, Pezo RC, et al. Novel Detection and Differential Utilization of a c-myc Transcriptional Block in Colon Cancer Chemoprevention. Cancer Res 2002; 62: 6006-10.

Fichera A, Little N, Dougherty U, Mustafi R, Cerda S, Li YC, et al. A Vitamin D Analogue Inhibits Colonic Carcinogenesis in the AOM/DSS Model. J Surg Res 2007; 142: 239-45.

https://doi.org/10.1016/j.jss.2007.02.038 DOI: https://doi.org/10.1016/j.jss.2007.02.038

Chen S, Bu D, Ma Y, Zhu J, Chen G, Sun L, et al. H19 Overexpression Induces Resistance to 1,25(OH)2D3 by Targeting VDR Through miR-675-5p in Colon Cancer Cells. Neoplasia 2017; 19: 226-36.

https://doi.org/10.1016/j.neo.2016.10.007 DOI: https://doi.org/10.1016/j.neo.2016.10.007

Murillo G, Mehta RG. Chemoprevention of chemically-in-duced mammary and colon carcinogenesis by 1α-hydroxy-vitamin D5. J Steroid Biochem Mol Biol 2005; 97: 129-36.

https://doi.org/10.1016/j.jsbmb.2005.06.008 DOI: https://doi.org/10.1016/j.jsbmb.2005.06.008

Ahearn TU, Shaukat A, Flanders WD, Rutherford RE, Bostick RM. A Randomized Clinical Trial of the Effects of Supplemental Calcium and Vitamin D3 on the APC/β-Catenin Pathway in the Normal Mucosa of Colorectal Adenoma Patients. Cancer Prev Res 2012; 5: 1247-56.

https://doi.org/10.1158/1940-6207.CAPR-12-0292 DOI: https://doi.org/10.1158/1940-6207.CAPR-12-0292

Liu S, Barry EL, Baron JA, Rutherford RE, Seabrook ME, Bostick RM. Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients. Mol Carcinog 2017; 56: 412-24.

https://doi.org/10.1002/mc.22504 DOI: https://doi.org/10.1002/mc.22504

Samanta S, Chatterjee M, Ghosh B, Rajkumar M, Rana A, Chatterjee M. Vanadium and 1, 25 (OH)2 vitamin D3 combination in inhibitions of 1,2, dimethylhydrazine-induced rat colon carcinogenesis. Biochim Biophys Acta 2008; 1780: 1106-14.

https://doi.org/10.1016/j.bbagen.2008.05.003 DOI: https://doi.org/10.1016/j.bbagen.2008.05.003

Pálmer HG, González-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, et al. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling. Journal of Cell Biology 2001; 154: 369-88.

https://doi.org/10.1083/jcb.200102028 DOI: https://doi.org/10.1083/jcb.200102028

Xu H, Posner GH, Stevenson M, Campbell FC. Apc MIN modulation of vitamin D secosteroid growth control. Carcinogenesis 2010; 31: 1434-41.

https://doi.org/10.1093/carcin/bgq098 DOI: https://doi.org/10.1093/carcin/bgq098

Xin Y, He L, Luan Z, Lv H, Yang H, Zhou Y, et al. E-cadherin Mediates the Preventive Effect of Vitamin D3 in Colitis-associated Carcinogenesis. Inflamm Bowel Dis 2017; 23: 1535-43.

https://doi.org/10.1097/MIB.0000000000001209 DOI: https://doi.org/10.1097/MIB.0000000000001209

Aguilera O, Pena C, Garcia JM, Larriba MJ, Ordonez-Moran P, Navarro D, et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1 ,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis 2007; 28: 1877-84.

https://doi.org/10.1093/carcin/bgm094 DOI: https://doi.org/10.1093/carcin/bgm094

Deevi RK, McClements J, McCloskey KD, Fatehullah A, Tkocz D, Javadi A, et al. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype. Oncotarget 2016; 7: 49042-64.

https://doi.org/10.18632/oncotarget.8863 DOI: https://doi.org/10.18632/oncotarget.8863

Franceschi RT, Linson CJ, Peter TC, Romano PR. Regulation of cellular adhesion and fibronectin synthesis by 1 alpha, 25-dihydroxyvitamin D3. J Biol Chem 1987; 262: 4165-71. DOI: https://doi.org/10.1016/S0021-9258(18)61327-4

Makishima M. Vitamin D Receptor As an Intestinal Bile Acid Sensor. Science 2002; 296: 1313-6.

https://doi.org/10.1126/science.1070477 DOI: https://doi.org/10.1126/science.1070477

Dıaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A. Apoptosis Is Induced by the Active Metabolite of Vitamin D3 and Its Analogue EB1089 in Colorectal Adenoma and Carcinoma Cells: Possible Implications for Prevention and Therapy. Cancer Res 2000; 60: 2304-12.

Bessler H, Djaldetti M. 1α,25-dihydroxyvitamin D3 modulates the interaction between immune and colon cancer cells. Biomed Pharmacother 2012; 66: 428-32.

https://doi.org/10.1016/j.biopha.2012.06.005 DOI: https://doi.org/10.1016/j.biopha.2012.06.005

Murillo G, Nagpal V, Tiwari N, Benya RV, Mehta RG. Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer. J Steroid Biochem Mol Biol 2010; 121: 403-7.

https://doi.org/10.1016/j.jsbmb.2010.03.009 DOI: https://doi.org/10.1016/j.jsbmb.2010.03.009

Meeker S, Seamons A, Paik J, Treuting PM, Brabb T, Grady WM, et al. Increased Dietary Vitamin D Suppresses MAPK Signaling, Colitis, and Colon Cancer. Cancer Res 2014; 74: 4398-408.

https://doi.org/10.1158/0008-5472.CAN-13-2820 DOI: https://doi.org/10.1158/0008-5472.CAN-13-2820

Hopkins MH, Owen J, Ahearn T, Fedirko V, Flanders WD, Jones DP, et al. Effects of Supplemental Vitamin D and Calcium on Biomarkers of Inflammation in Colorectal Adenoma Patients: A Randomized, Controlled Clinical Trial. Cancer Prev Res 2011; 4: 1645-54.

https://doi.org/10.1158/1940-6207.CAPR-11-0105 DOI: https://doi.org/10.1158/1940-6207.CAPR-11-0105

Iseki K, Tatsuta M, Uehara H, IIshi H, Yano H, Sakai N, et al. Inhibition of angiogenesis as a mechanism for inhibition by Lα‐hydroxyvitamin D3 and 1,25‐dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats. Int J Cancer 1999; 81: 730-3.

https://doi.org/10.1002/(sici)1097-0215(19990531)81:5<730::aid-ijc11>3.0.co;2-q DOI: https://doi.org/10.1002/(SICI)1097-0215(19990531)81:5<730::AID-IJC11>3.0.CO;2-Q

Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ. 1α,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther 2007; 6: 1433-9.

https://doi.org/10.1158/1535-7163.MCT-06-0677 DOI: https://doi.org/10.1158/1535-7163.MCT-06-0677

Chen S, Zhu J, Zuo S, Ma J, Zhang J, Chen G, et al. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells. Biochem Biophys Res Commun 2015; 468: 130-5.

https://doi.org/10.1016/j.bbrc.2015.10.146 DOI: https://doi.org/10.1016/j.bbrc.2015.10.146

Nguyen H, Duong H. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review). Oncol Lett 2018; 16: 9-18.

https://doi.org/10.3892/ol.2018.8679 DOI: https://doi.org/10.3892/ol.2018.8679

Dovnik A, Dovnik NF. Vitamin D and Ovarian Cancer: Systematic Review of the Literature with a Focus on Molecular Mechanisms. Cells 2020; 9: 335.

https://doi.org/10.3390/cells9020335 DOI: https://doi.org/10.3390/cells9020335

Moreno J, Krishnan AV, Feldman D. Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer. J Steroid Biochem Mol Biol 2005; 97: 31-6.

https://doi.org/10.1016/j.jsbmb.2005.06.012 DOI: https://doi.org/10.1016/j.jsbmb.2005.06.012

Krishnan AV, Feldman D. Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer 2010; 17: R19-38.

https://doi.org/10.1677/ERC-09-0139 DOI: https://doi.org/10.1677/ERC-09-0139

Krishnan AV, Swami S, Feldman D. Vitamin D and breast cancer: Inhibition of estrogen synthesis and signaling. J Steroid Biochem Mol Biol 2010; 121: 343-8.

https://doi.org/10.1016/j.jsbmb.2010.02.009 DOI: https://doi.org/10.1016/j.jsbmb.2010.02.009

Krishnan AV, Swami S, Feldman D. The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer. Steroids 2012; 77: 1107-12.

https://doi.org/10.1016/j.steroids.2012.06.005 DOI: https://doi.org/10.1016/j.steroids.2012.06.005

Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, et al. Vitamin D, Calcium Supplementation, and Colorectal Adenomas: Results of a Randomized Trial. J Natl Cancer Inst 2003; 95: 1765-71.

https://doi.org/10.1093/jnci/djg110 DOI: https://doi.org/10.1093/jnci/djg110

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85: 1586-91.

https://doi.org/10.1093/ajcn/85.6.1586 DOI: https://doi.org/10.1093/ajcn/85.6.1586

Bises G, Kállay E, Weiland T, Wrba F, Wenzl E, Bonner E, et al. 25-Hydroxyvitamin D3 -1α-hydroxylase Expression in Normal and Malignant Human Colon. J Histochem Cytochem 2004; 52: 985-9.

https://doi.org/10.1369/jhc.4B6271.2004 DOI: https://doi.org/10.1369/jhc.4B6271.2004

Matusiak D. Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1 -Hydroxylase in Normal and Malignant Human Colon. Cancer Epidemiol Biomarkers Prev 2005; 14: 2370-6.

https://doi.org/10.1158/1055-9965.EPI-05-0257 DOI: https://doi.org/10.1158/1055-9965.EPI-05-0257

Horváth HC, Lakatos P, Kósa JP, Bácsi K, Borka K, Bises G, et al. The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis. J Histochem Cytochem 2010; 58: 277-85.

https://doi.org/10.1369/jhc.2009.954339 DOI: https://doi.org/10.1369/jhc.2009.954339

Lopes N, Sousa B, Martins D, Gomes M, Vieira D, Veronese LA, et al. Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions. BMC Cancer 2010; 483.

https://doi.org/10.1186/1471-2407-10-483 DOI: https://doi.org/10.1186/1471-2407-10-483

Hendrickson WK, Flavin R, Kasperzyk JL, Fiorentino M, Fang F, Lis R, et al. Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression. J Clin Oncol 2011; 29: 2378-85.

https://doi.org/10.1200/JCO.2010.30.9880 DOI: https://doi.org/10.1200/JCO.2010.30.9880

Brożyna AA, Jóźwicki W, Jochymski C, Slominski AT. Decreased expression of CYP27B1 correlates with the increased aggressiveness of ovarian carcinomas. Oncol Rep 2015; 33: 599-606.

https://doi.org/10.3892/or.2014.3666 DOI: https://doi.org/10.3892/or.2014.3666

Mittal MK, Myers JN, Misra S, Bailey CK, Chaudhuri G. In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells. Biochem Biophys Res Commun 2008; 372: 30-4.

https://doi.org/10.1016/j.bbrc.2008.04.187 DOI: https://doi.org/10.1016/j.bbrc.2008.04.187

Stambolsky P, Tabach Y, Fontemaggi G, Weisz L, Maor-Aloni R, Sigfried Z, et al. Modulation of the Vitamin D3 Response by Cancer-Associated Mutant p53. Cancer Cell 2010; 17: 273-85.

https://doi.org/10.1016/j.ccr.2009.11.025 DOI: https://doi.org/10.1016/j.ccr.2009.11.025

Komagata S, Nakajima M, Takagi S, Mohri T, Taniya T, Yokoi T. Human CYP24 Catalyzing the Inactivation of Calcitriol Is Post-Transcriptionally Regulated by miR-125b. Mol Pharmacol 2009; 76: 702-9.

https://doi.org/10.1124/mol.109.056986 DOI: https://doi.org/10.1124/mol.109.056986

Downloads

Published

2021-11-15

How to Cite

Herdian, F., Radityamurti, F., Permata, T. B. M. ., Handoko, H., Kodrat, H., Nuryadi, E., Wibowo, H., & Gondhowiardjo , S. . (2021). The Role of Vitamin D in Preventing Colorectal Carcinogenesis: A Review of Molecular Mechanisms. Journal of Pharmacy and Nutrition Sciences, 11, 123–133. https://doi.org/10.29169/1927-5951.2021.11.15

Issue

Section

Articles
Loading...