Issue
Vitamin D can be used as a supplement against cancer stem cells
Corresponding Author(s) : Nadir Koçak
Cellular and Molecular Biology,
Vol. 64 No. 12: Issue 12
Abstract
Cancer is standing like a bottomless pit or a black hole in front of mankind. Scientists are trying all possible ways to find a solution against to cancer. As known, cancer is a phenomenon fed from internal dynamics. One of internal dynamic is cancer stem cells that are involved in the formation and development of cancer. Because of these dynamics, scientists began to search solution inside of the body. Another internal dynamic is vitamin D and it is not only important in calcium homeostasis but also it is important for cell proliferation, differentiation, and apoptosis. In this study, we investigated the effect of vitamin D on cancer stem cells that sorted from MCF-7 cell line and on HEK293 cell line as control. Our results showed that calcitriol treatment reduced the number of CSC (Cancer Stem Cell) in the MCF-7 cell while increased in HEK293 cell population. Gene expression analyses showed that effect of calcitriol on apoptosis plays an important role in this reduction. Deficiency or unavailability of vitamin D may take a role in the pathogenesis of breast cancer.
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- - Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J. Clin 2010; 60:277–300.
- - Visvader JE, Lindeman GJ. Cancer stem cells in solid tumors: accumulatingevidence and unresolved questions. Nat. Rev. Cancer 2008; 8(10): 755–768.
- - Clevers H. The cancer stem cell: premises, promises, and challenges. Nat.Med. 2011: 17(3): 313–319.
- - Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identiï¬cation of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100:3983–3988.
- - Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, at al. Identiï¬cation of a cancer stem cell in human brain tumors. Cancer Research2003; 63:5821–5828.
- - Vermeulen L, De Sousa E, Melo F, van der Heijden M, Cameron K, de Jong H, et al. Wnt activity deï¬nes colon cancer stem cells and is regulated by the microenvironment.Nat Cell Biol 2010; 12:468–476.
- - Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells– old concepts, new insights. Cell Death Differ 2008; 15:947–958.
- - Nair R, Maseeh A, Vitamin D: The "sunshine” vitamin. J Pharmacol Pharmacother 2012; 3(2):118-126.
- - Chakraborti CK. Vitamin D as a promising anticancer agent. Indian J Pharmacol 2011; 43(2):113-120.
- - Bikle D. Nonclassic Actions of Vitamin D. J Clin Endocrinol Metab 2009; 94(1): 2634
- - Colston K, Colston MJ, Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptor and inhibition of cell growth in culture. Endocrinology 1981 108(3):1083-1086
- - Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch. Biochem. Biophys 2012; 523:123–133.
- - Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstufy A, Luderer L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 2008; 29:726–776.
- - Deeb KK, Trump D L, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Rev. Cancer 2007; 7:684–700.
- - Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 2012; 441:61–76.
- - Haussler M R, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh JC, et al. Molecular mechanisms of vitamin D action. Calcif Tissue Int 2013; 92:77–98.
- - Jones G. Vitamin D analogs. Endocrinol Metab Clin North Am 2010; 39:447–472.
- - Krishnan AV, Feldman D. Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer 2010; 17:19–38.
- - Pereira F, Larriba MJ, Munoz A. Vitamin D and colon cancer. Endocr Relat Cancer 2012; 19:51–71.
- - Larriba MJ, Munoz A. SNAIL versus vitamin D receptor expression in colon cancer: therapeutics implications. Br J Cancer 2005; 92:985–989.
- - 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; 85:1586-1591.
- - Brozek W, Manhardt T, Kallay E, Peterlik M, Cross HS. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis. Cancers (Basel) 2012 4(3):763-776.
- - Tanqpricha V, Spina C, Yao M, Chen TC, Wolfe MM, Holick MF. Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice, J Nurt 2005; 135(10):2350-2354.
- - Al Nozha OM, Vitamin D and extra-skeletal health: causality or sequence. Int J Health Sci (Qassim) 2016; 10(3):443-452.
- - Colston KW, Hansen CM. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 2002;9(1):45–59.
- - Welsh J, Wietzke JA, Zinser GM, Smyczek S, Romu S, Tribble E, et al. Impact of the vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. J Steroid Biochem Mol Biol 2002;83(1–5):85–92.
- - Santoz-Martinez N, Diaz L, Ordaz-Rosado D, Garcia-Quiroz J, Barrera D, Avila E, et al. Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: A potential new therapeutic approach. BMC Cancer 2014; 14:230.
- - Pervin S, Hewison M, Braga M, Tran L, Chun R, Karam A, et al. Down-regulation of vitamin D receptor in mammospheres: implications for vitamin D resistance in breast cancer and potential for combination therapy. PLoS ONE 2013; 8(1):e53287.
- - So JY, Lee HJ, Smolarek AK, Paul S, Wang CX, Maehr H, et al. A novel Gemini vitamin D analog represses the expression of a stem cell marker CD44 in breast cancer. Mol Pharmacol 2011; 79:360–367.
- - Maund SL, Barclay WW, Hower LD, Axanova LS, Sui G, Hipp JD, et al. Interleukin"‘1α mediates the antiproliferative effects of 1,25"‘dihydroxyvitamin D3 in prostate progenitor/stem cells. Cancer Res 2011; 71:5276–5286.
References
- Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J. Clin 2010; 60:277–300.
- Visvader JE, Lindeman GJ. Cancer stem cells in solid tumors: accumulatingevidence and unresolved questions. Nat. Rev. Cancer 2008; 8(10): 755–768.
- Clevers H. The cancer stem cell: premises, promises, and challenges. Nat.Med. 2011: 17(3): 313–319.
- Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identiï¬cation of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100:3983–3988.
- Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, at al. Identiï¬cation of a cancer stem cell in human brain tumors. Cancer Research2003; 63:5821–5828.
- Vermeulen L, De Sousa E, Melo F, van der Heijden M, Cameron K, de Jong H, et al. Wnt activity deï¬nes colon cancer stem cells and is regulated by the microenvironment.Nat Cell Biol 2010; 12:468–476.
- Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells– old concepts, new insights. Cell Death Differ 2008; 15:947–958.
- Nair R, Maseeh A, Vitamin D: The "sunshine” vitamin. J Pharmacol Pharmacother 2012; 3(2):118-126.
- Chakraborti CK. Vitamin D as a promising anticancer agent. Indian J Pharmacol 2011; 43(2):113-120.
- Bikle D. Nonclassic Actions of Vitamin D. J Clin Endocrinol Metab 2009; 94(1): 2634
- Colston K, Colston MJ, Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptor and inhibition of cell growth in culture. Endocrinology 1981 108(3):1083-1086
- Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch. Biochem. Biophys 2012; 523:123–133.
- Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstufy A, Luderer L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 2008; 29:726–776.
- Deeb KK, Trump D L, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Rev. Cancer 2007; 7:684–700.
- Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 2012; 441:61–76.
- Haussler M R, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh JC, et al. Molecular mechanisms of vitamin D action. Calcif Tissue Int 2013; 92:77–98.
- Jones G. Vitamin D analogs. Endocrinol Metab Clin North Am 2010; 39:447–472.
- Krishnan AV, Feldman D. Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer 2010; 17:19–38.
- Pereira F, Larriba MJ, Munoz A. Vitamin D and colon cancer. Endocr Relat Cancer 2012; 19:51–71.
- Larriba MJ, Munoz A. SNAIL versus vitamin D receptor expression in colon cancer: therapeutics implications. Br J Cancer 2005; 92:985–989.
- 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; 85:1586-1591.
- Brozek W, Manhardt T, Kallay E, Peterlik M, Cross HS. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis. Cancers (Basel) 2012 4(3):763-776.
- Tanqpricha V, Spina C, Yao M, Chen TC, Wolfe MM, Holick MF. Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice, J Nurt 2005; 135(10):2350-2354.
- Al Nozha OM, Vitamin D and extra-skeletal health: causality or sequence. Int J Health Sci (Qassim) 2016; 10(3):443-452.
- Colston KW, Hansen CM. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 2002;9(1):45–59.
- Welsh J, Wietzke JA, Zinser GM, Smyczek S, Romu S, Tribble E, et al. Impact of the vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. J Steroid Biochem Mol Biol 2002;83(1–5):85–92.
- Santoz-Martinez N, Diaz L, Ordaz-Rosado D, Garcia-Quiroz J, Barrera D, Avila E, et al. Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: A potential new therapeutic approach. BMC Cancer 2014; 14:230.
- Pervin S, Hewison M, Braga M, Tran L, Chun R, Karam A, et al. Down-regulation of vitamin D receptor in mammospheres: implications for vitamin D resistance in breast cancer and potential for combination therapy. PLoS ONE 2013; 8(1):e53287.
- So JY, Lee HJ, Smolarek AK, Paul S, Wang CX, Maehr H, et al. A novel Gemini vitamin D analog represses the expression of a stem cell marker CD44 in breast cancer. Mol Pharmacol 2011; 79:360–367.
- Maund SL, Barclay WW, Hower LD, Axanova LS, Sui G, Hipp JD, et al. Interleukin"‘1α mediates the antiproliferative effects of 1,25"‘dihydroxyvitamin D3 in prostate progenitor/stem cells. Cancer Res 2011; 71:5276–5286.