Int J Oncol. 2013 Nov;43(5):1691-700. doi: 10.3892/ijo.2013.2089.

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

Kim S1, Chun SY, Lee DH, Lee KS, Nam KS.

1Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju 780-714, Republic of Korea.

 

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.

PMID: 24008507

 

Supplementary

Deep-sea water (DSW) defined as sea water from a depth of more than 200 meters is rich in minerals such as calcium (Ca), magnesium (Mg), potassium (K), sodium (Na), zinc (Zn), etc. Due to its high productivity, large quantity, and enrichment in natural nutrients and minerals, the utilization of DSW has drawn much interest in many fields including aquaculture, agriculture, food processing and cosmetics (1). More recently, scientific efforts to establish the health benefits of DSW have been made to extend its application towards medical fields. As part of these efforts, this study evaluated the effects of DSW on the metastatic potential of two human breast cancer cell lines (MDA-MB-231 and MCF-7) in relation to their tumor cell migration, TGF-β, and its relevant signaling pathway, such as Wnt5a, CD44 and MMPs.

MDA-MB-231 human breast cancer cells provide a model of aggressive human breast cancer and DSW treatment significantly inhibited their migratory ability in a wound healing assay. This inhibitory effect of DSW appeared to be mediated through TGF-β and Wnt5a signaling, thus resulting in the attenuated expression of CD44. We then further investigated the preventive effect of DSW on tumor promotor (TPA)-induced invasive/metastatic tumor features in non-invasive MCF-7 cells, and 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. Although the mechanism underlying the DSW-mediated suppression on tumor migration and invasion were not fully elucidated in this study, this is the first study to provide an important clue for a possible mechanism of the inhibitory effects of DSW on the Wnt signaling pathway, which aids in mediating cell migration and invasion in coordination with the TGF-β signaling pathway.

It is presumed that these anti-tumor activities of DSW may be derived from the combined ionic action of several minerals such as calcium (Ca), magnesium (Mg) and potassium (K) in DSW. Among these minerals, calcium and magnesium may play important roles in mediating the inhibition of metastasis because they are the main mineral ions present in DSW; the concentration of calcium is approximately 100 mg/L, while the amount of magnesium is approximately 300 mg/L in 1,500 hardness DSW. Although the deficiency of magnesium and/or calcium levels has been linked to increased risks of cancer and metastasis (2,3), more recent study emphasized a need for both minerals in reducing the risk of cancer (4). Thus, DSW may be a beneficial source that provides the proper ratio of calcium to magnesium, leading to the synergetic effects via the interrelationship between magnesium and calcium.

References

  1. Nakasone T and Akeda S: The application of deep sea water in Japan. UJNR Technical Report 28: 69-75, 1999.
  2. 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.
  3. 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.
  4. 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.

Acknowledgments

This work was supported by the Ministry of Ocean and Fisheries, Korea.

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