Anti-Osteoclastic Effect of Zinc Studied in MCF-7 Induced Osteoclastogenesis
Bone which a key structural support of the body, undergoes dynamic micro structural remodelling all over life to control automatic stress and calcium requirement in the body. A number of risk factors including oxidative stress, apoptosis and abnormal intracellular Ca2+ metabolism have been postulated to play a function in the inception and progress of bone osteolysis. Cancer cells establish a tight relationship with the host tissue, secreting factors that stimulate or inhibit bone cells, receiving signals generated from the bone remodelling activity, and displaying some features of bone cells. This interplay between tumour and bone cells alters the physiological bone remodelling, leading to the generation of a vicious cycle that promotes bone metastasis growth. Zinc is one of the most relevant minerals to human health, because of its antioxidant properties. The present study was aimed to investigate protective role of zinc against bone metastasis. In the present study, TRAP positive multinucleated cell count was low compared to CM treated cells. Zinc treatment suppressed MCF-7 induced mRNA levels of cytoplasmic 1 (Nfatc1), TRAP and Cathepsin-K. Hence, it can be concluded that zinc decreases osteoclastogenesis induced by MCF-7 cells.
Keywords: Oxidative stress; Metastasis; Bone remodelling; Zinc.
2. Jurowski K, Szewczyk B, Biological consequences of zinc deficiency in the pathomechanisms of selected diseases, Journal of Biological Inorganic Chemistry, 2014; 19: 1069–1079.
3. Foster M, Chu A, Zinc transporter gene expression and glycemic control in post-menopausal women with type 2 diabetes mellitus, Journal of Trace Elements in Medicine and Biology 2014; 28: 448–452.
4. Fung, EB, Gildengorin G, Zinc status affects glucose homeostasis and insulin secretion in patients with thalassemia, Nutrients 2015; 7: 4296–4307.
5. Jansen J, Rosenkranz E, Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of zinc, 2012, 23: 1458–1466.
6. Cruz JBF, Soares HF, Uma revisão sobre o zinco, Ensaios Ciência Ciências Biológicas Agrárias Saúde, 2011; 15: 207–222.
7. Homma K, FujisawaT,SOD1 as a molecular switch for initiating the homeostatic ER stress response under zinc deficiency, Molecular Cell, 2013; 52: 75–86.
8. Maret W, Krezel, A, Cellular zinc and redox buffering capacity of metallothionein/thionein in health and disease, Molecular Medicine, 2007; 13:371–375.
9. Ozcelik D, Nazıroglu M, Zinc supplementation attenuates metallothionein and oxidative stress changes in kidney of streptozotocin-induced diabetic rats, Biological Trace Element Research, 2012; 150: 342–349.
10. Butterfield DA, Domenico FB, Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain Biochimica et Biophysica Acta, 2014; 1824, 1693–1706.
11. Feng B, Ruiz MA, Oxidative-stress-induced epigenetic changes in chronic diabetic complications, Canadian Journal of Physiology and Pharmacology, 2013; 91:213–220.
12. Pisoschi AM, Pop A, The role of antioxidants in the chemistry of oxidative stress: A review, European Journal of Medicinal Chemistry, 2015; 97:55–74.
13. Prabasheela B, Singh AK, Association between Antioxidant Enzymes and Breast, Recent Research in Science and Technology, 2011; 3: 93–95.
14. Coleman RE, Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treatment Reviews, 2001; 27: 165–176.
15. Mundy, G.R, Metastasis to bone: Causes, consequences and therapeutic opportunities, Nature Reviews Cancer, 2002; 2: 584–593.
16. Selvaggi G, Scagliotti GV, Management of bone metastases in cancer: A review, Critical Reviews in Oncology/Hematology, 2005; 56: 365–378.
17. Clines GA, Guise TA, Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone, Endocrine-Related Cancer, 2005; 12:549e583.
18. Mastro AM, Gay CV, Welch, DR, The skeleton as a unique environment for breast cancer cells, Clinical & Experimental Metastasis 2003; 20: 275–284.
19. Guise TA, Mohammad, KS, Clines G, Stebbins EG, Wong, D.H, Higgins LS, Vessella R, Corey, E, Padalecki S, Suva L, et al, Basic mechanisms responsible for osteolytic and osteoblastic bone metastases, Clinical cancer research: an official journal of the American Association for Cancer Research, 2006; 12:6213s–6216s.
20. Virk MS, Lieberman JR, Tumor metastasis to bone, Arthritis Research & Therapy, 2007; 9 (Suppl. 1), S5.
21. Chu GC, Chung LW, RANK-mediated signaling network and cancer metastasis, Cancer Metastasis Reviews, 2014; 33(2–3): 497–509.
22. Nagy V, Penninger JM,The RANKL-RANK story, Gerontology, 2015; 16(6): 534–42.
23. Clohisy DR, Palkert D, Ramnaraine ML, Pekurovsky I, Oursler MJ, Human breast cancer induces osteoclast activation and increases the number of osteoclasts at sites of tumor osteolysis, Journal of Orthopaedic Research, 1996; 14(3):396-402.
24. Hie M, Tsukamoto I, Administration of zinc inhibits osteoclastogenesis through the suppression of RANK expression in bone, European Journal of Pharmacology, 2011; 668:140–146.
25. Park KH et al, Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signalling pathway, Cell Communication and Signalling 2013; 11:74.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).