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Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.
MedLine Citation:
PMID:  24032073     Owner:  NLM     Status:  Publisher    
BACKGROUND: Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H(+) ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model.
METHODS: Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging.
RESULTS: PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis.
CONCLUSION: PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival indicating acidity plays a significant role in growth and invasion in-vivo.
Arig Ibrahim-Hashim; Jonathan W Wojtkowiak; Maria de Lourdes Coelho Ribeiro; Veronica Estrella; Kate M Bailey; Heather H Cornnell; Robert A Gatenby; Robert J Gillies
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Publication Detail:
Journal Detail:
Title:  Journal of cancer science & therapy     Volume:  Suppl 1     ISSN:  1948-5956     ISO Abbreviation:  J Cancer Sci Ther     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2013-9-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101526958     Medline TA:  J Cancer Sci Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Imaging, H. Lee Moffitt Cancer Center Tampa, FL 33612.
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