Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines

Kim,Soyoung; Chun,So-Young; Lee,Do-Hyung; Lee,Kyu-Shik; Nam,Kyung-Soo

doi:10.3892/ijo.2013.2089

Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines

Authors:
- Soyoung Kim
- So-Young Chun
- Do-Hyung Lee
- Kyu-Shik Lee
- Kyung-Soo Nam
View Affiliations

Affiliations: Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju 780-714, Republic of Korea
Published online on: September 4, 2013 https://doi.org/10.3892/ijo.2013.2089
Pages: 1691-1700

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Recently, the scientific community has begun to establish the health benefits of deep-sea water (DSW) due to its enrichment in nutrients and minerals. In this study, we investigated the effects of deep-sea water (DSW) on the metastatic potential of two human breast cancer cell lines exhibiting highly different phenotypes. MDA-MB-231 cells exhibit invasive/metastatic tumor features with rapid migration ability and high endogenous expression of TGF-β and Wnt5a. DSW treatment significantly inhibits their migratory ability in a wound-healing assay. This inhibitory effect of DSW appears to be mediated through TGF-β and Wnt5a signaling, resulting in attenuated expression of CD44. We further investigated the preventive effect of DSW on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasive/metastatic tumor features in non-invasive MCF-7 cells. Similar to the inhibitory effects shown in MDA-MB-231 cells, we observed that DSW treatment resulted in the inhibition of TPA-induced migration and MMP-9 activity with a concomitant decrease in mRNA levels of MMP-9, TGF-β, Wnt5a and Wnt3a. Taken together, our data show that DSW has inhibitory effects on breast cancer invasion/metastasis, suggesting that DSW has some promise in improving cancer survival by preventing tumor metastasis.

View Figures

View References

1.	Nakasone T and Akeda S: The application of deep sea water in Japan. UJNR Technical Report. 28:69–75. 1999.
2.	Shon YH, Kim JS and Nam KS: Inhibitory effect of Deep-sea water on cytochrome P450 1A1, aromatase, and MMP-9. J Life Sci. 18:503–508. 2008. View Article : Google Scholar
3.	Hwang HS, Kim SH, Yoo YG, et al: Inhibitory effect of deep-sea water on differentiation of 3T3-L1 adipocytes. Mar Biotechnol (NY). 11:161–168. 2009. View Article : Google Scholar : PubMed/NCBI
4.	Radhakrishnan G, Yamamoto M, Maeda H, et al: Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression. Biochem Biophys Res Commun. 387:25–30. 2009. View Article : Google Scholar : PubMed/NCBI
5.	Lee KS, Shin JS, Kwon YS, Moon DS and Nam KS: Suppression of cancer progression and metastasis in HT-29 human colorectal adenocarcinoma by deep sea water. Biotechnol Bioproc Eng. 18:194–200. 2013. View Article : Google Scholar
6.	Kohli GS, Bhargava A, Goel H, et al: Serum magnesium levels in patients with head and neck cancer. Magnesium. 8:77–86. 1989.PubMed/NCBI
7.	Lappe JM, Travers-Gustafson D, Davies KM, Recker RR and Heaney RP: Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 85:1586–1591. 2007.PubMed/NCBI
8.	Nasulewicz A, Wietrzyk J, Wolf FI, et al: Magnesium deficiency inhibits primary tumor growth but favors metastasis in mice. Biochim Biophys Acta. 1739:26–32. 2004. View Article : Google Scholar : PubMed/NCBI
9.	Sartori S, Nielsen I, Tassinari D, et al: Serum and erythrocyte magnesium concentrations in solid tumours: relationship with stage of malignancy. Magnes Res. 5:189–192. 1992.PubMed/NCBI
10.	Wu K, Willett WC, Fuchs CS, Colditz GA and Giovannucci EL: Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst. 94:437–446. 2002. View Article : Google Scholar : PubMed/NCBI
11.	Gamucci T, D’Ottavio AM, Magnolfi E, et al: Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer. Br J Cancer. 97:1040–1045. 2007. View Article : Google Scholar : PubMed/NCBI
12.	Padua D and Massague J: Roles of TGFbeta in metastasis. Cell Res. 19:89–102. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Shariat SF, Shalev M, Menesses-Diaz A, et al: Preoperative plasma levels of transforming growth factor beta(1) (TGF-beta(1)) strongly predict progression in patients undergoing radical prostatectomy. J Clin Oncol. 19:2856–2864. 2001.
14.	Tsushima H, Ito N, Tamura S, et al: Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer. Clin Cancer Res. 7:1258–1262. 2001.PubMed/NCBI
15.	Yang YA, Dukhanina O, Tang B, et al: Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest. 109:1607–1615. 2002. View Article : Google Scholar : PubMed/NCBI
16.	Yin JJ, Selander K, Chirgwin JM, et al: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 103:197–206. 1999. View Article : Google Scholar : PubMed/NCBI
17.	Howe LR and Brown AM: Wnt signaling and breast cancer. Cancer Biol Ther. 3:36–41. 2004. View Article : Google Scholar : PubMed/NCBI
18.	Katoh M: Transcriptional mechanisms of WNT5A based on NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades. Int J Mol Med. 23:763–769. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Lejeune S, Huguet EL, Hamby A, Poulsom R and Harris AL: Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Clin Cancer Res. 1:215–222. 1995.PubMed/NCBI
20.	Smith K, Bui TD, Poulsom R, Kaklamanis L, Williams G and Harris AL: Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer. Br J Cancer. 81:496–502. 1999. View Article : Google Scholar : PubMed/NCBI
21.	Bittner M, Meltzer P, Chen Y, et al: Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature. 406:536–540. 2000. View Article : Google Scholar : PubMed/NCBI
22.	Weeraratna AT, Jiang Y, Hostetter G, et al: Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 1:279–288. 2002. View Article : Google Scholar : PubMed/NCBI
23.	Dissanayake SK, Wade M, Johnson CE, et al: The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition. J Biol Chem. 282:17259–17271. 2007. View Article : Google Scholar : PubMed/NCBI
24.	Dietrich A, Tanczos E, Vanscheidt W, Schopf E and Simon JC: High CD44 surface expression on primary tumours of malignant melanoma correlates with increased metastatic risk and reduced survival. Eur J Cancer. 33:926–930. 1997. View Article : Google Scholar : PubMed/NCBI
25.	O’Connell MP, Fiori JL, Xu M, et al: The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 29:34–44. 2010.PubMed/NCBI
26.	Nabeshima K, Inoue T, Shimao Y and Sameshima T: Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int. 52:255–264. 2002. View Article : Google Scholar : PubMed/NCBI
27.	Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H and Itohara S: Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res. 58:1048–1051. 1998.PubMed/NCBI
28.	Perou CM, Sorlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI
29.	Subramaniam DS and Isaacs C: Utilizing prognostic and predictive factors in breast cancer. Curr Treat Options Oncol. 6:147–159. 2005. View Article : Google Scholar : PubMed/NCBI
30.	Klemm F, Bleckmann A, Siam L, et al: beta-catenin-independent WNT signaling in basal-like breast cancer and brain metastasis. Carcinogenesis. 32:434–442. 2011. View Article : Google Scholar : PubMed/NCBI
31.	Kao J, Salari K, Bocanegra M, et al: Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One. 4:e61462009.PubMed/NCBI
32.	Lei X, Yang J, Nichols RW and Sun LZ: Abrogation of TGFbeta signaling induces apoptosis through the modulation of MAP kinase pathways in breast cancer cells. Exp Cell Res. 313:1687–1695. 2007. View Article : Google Scholar : PubMed/NCBI
33.	Dumont N, Bakin AV and Arteaga CL: Autocrine transforming growth factor-beta signaling mediates Smad-independent motility in human cancer cells. J Biol Chem. 278:3275–3285. 2003. View Article : Google Scholar : PubMed/NCBI
34.	Anastas JN and Moon RT: WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 13:11–26. 2013. View Article : Google Scholar : PubMed/NCBI
35.	Matsuda Y, Schlange T, Oakeley EJ, Boulay A and Hynes NE: WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth. Breast Cancer Res. 11:R322009. View Article : Google Scholar : PubMed/NCBI
36.	Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW and Jaattela M: Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J Biol Chem. 277:30738–30745. 2002. View Article : Google Scholar : PubMed/NCBI
37.	Cui Y and Rohan TE: Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomarkers Prev. 15:1427–1437. 2006. View Article : Google Scholar : PubMed/NCBI
38.	Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA and Willett WC: Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst. 94:1301–1311. 2002. View Article : Google Scholar : PubMed/NCBI
39.	Benito E, Stiggelbout A, Bosch FX, et al: Nutritional factors in colorectal cancer risk: a case-control study in Majorca. Int J Cancer. 49:161–167. 1991. View Article : Google Scholar : PubMed/NCBI
40.	Negri E, La Vecchia C, D’Avanzo B and Franceschi S: Calcium, dairy products, and colorectal cancer. Nutr Cancer. 13:255–262. 1990. View Article : Google Scholar
41.	Lajer H and Daugaard G: Cisplatin and hypomagnesemia. Cancer Treat Rev. 25:47–58. 1999. View Article : Google Scholar
42.	Wark PA, Lau R, Norat T and Kampman E: Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis. Am J Clin Nutr. 96:622–631. 2012. View Article : Google Scholar : PubMed/NCBI
43.	Maier JA, Nasulewicz-Goldeman A, Simonacci M, Boninsegna A, Mazur A and Wolf FI: Insights into the mechanisms involved in magnesium-dependent inhibition of primary tumor growth. Nutr Cancer. 59:192–198. 2007. View Article : Google Scholar : PubMed/NCBI
44.	Dai Q, Shrubsole MJ, Ness RM, et al: The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am J Clin Nutr. 86:743–751. 2007.PubMed/NCBI
45.	Jang JY, Jeon YK and Kim CW: Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells. BMC Cancer. 10:3912010. View Article : Google Scholar : PubMed/NCBI
46.	Kang JH, Song KH, Jeong KC, et al: Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells. BMC Cancer. 11:3342011. View Article : Google Scholar : PubMed/NCBI
47.	Li Y and Sarkar FH: Gene expression profiles of genistein-treated PC3 prostate cancer cells. J Nutr. 132:3623–3631. 2002.PubMed/NCBI
48.	Suzuki A, Ozono K, Kubota T, Kondou H, Tachikawa K and Michigami T: PTH/cAMP/PKA signaling facilitates canonical Wnt signaling via inactivation of glycogen synthase kinase-3beta in osteoblastic Saos-2 cells. J Cell Biochem. 104:304–317. 2008. View Article : Google Scholar : PubMed/NCBI
49.	Takeuchi E, Tanaka T, Umemoto E, et al: VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients. Arthritis Res. 4:R102002. View Article : Google Scholar