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Cancer Med. 2017 Jul;6(7):1720-1729. doi: 10.1002/cam4.1032. Epub 2017 May 29.

Tris-base buffer: a promising new inhibitor for cancer progression and metastasis.

Author information

1
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, Florida.
2
Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida.
3
Department of Radiology, H. Lee Moffitt Cancer Center, Tampa, Florida.

Abstract

Neutralizing tumor external acidity with oral buffers has proven effective for the prevention and inhibition of metastasis in several cancer mouse models. Solid tumors are highly acidic as a result of high glycolysis combined with an inadequate blood supply. Our prior work has shown that sodium bicarbonate, imidazole, and free-base (but not protonated) lysine are effective in reducing tumor progression and metastasis. However, a concern in translating these results to clinic has been the presence of counter ions and their potential undesirable side effects (e.g., hypernatremia). In this work, we investigate tris(hydroxymethyl)aminomethane, (THAM or Tris), a primary amine with no counter ion, for its effects on metastasis and progression in prostate and pancreatic cancer in vivo models using MRI and bioluminescence imaging. At an ad lib concentration of 200 mmol/L, Tris effectively inhibited metastasis in both models and furthermore led to a decrease in the expression of the major glucose transporter, GLUT-1. Our results also showed that Tris-base buffer (pH 8.4) had no overt toxicity to C3H mice even at higher doses (400 mmol/L). In conclusion, we have developed a novel therapeutic approach to manipulate tumor extracellular pH (pHe) that could be readily adapted to a clinical trial.

KEYWORDS:

Acidosis; GLUT-1; Tris-base; buffer therapy; metastasis; pancreatic cancer; prostate cancer

PMID:
28556628
PMCID:
PMC5504318
DOI:
10.1002/cam4.1032
[Indexed for MEDLINE]
Free PMC Article

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