Suppression of cancer progression and metastasis in HT-29 human colorectal adenocarcinomas by deep sea water

In this investigation, we studied the effects of deep sea water (DSW) on cancer progression and metastasis in HT-29 human colorectal adenocarcinomas. The protein expression of tumor necrosis factor-α (TNF-α)-induced cyclooxygenase-2 (COX-2), which is an important enzyme in cancer progression, invasion and metastasis, was lessened by DSW in the hardness range of 200 ∼ 1,500. However, COX-2 transcription was not changed by DSW. TPA-induced expression of urokinase plasminogen activator (uPA), an inducer of cancer metastasis, was also suppressed by DSW in a hardness-dependent manner. In contrast, uPA receptor (uPAR) expression was not changed by DSW treatment. The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mRNA level of transforming growth factor-β (TGF-β), which induces cancer proliferation and metastasis, was decreased by treatment with DSW. We also explored the effects of hardness 1,500 mineral water prepared with exogenous Mg2+ or Mg2+/Ca2+ mixture (concentration ratio 3:1). Mineral water did not inhibit COX-2 protein and uPA mRNA expression but reversed uPAR and TGF-β transcription. The results suggest that DSW may prevent cancer proliferation and metastasis via inhibition of COX-2, uPA, uPAR and TGF-β expression in HT-29 colorectal cancer cells, but the COX-2 and uPA down-regulation is independent of the concentration of Mg2+ in DSW.