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3ВОДНЫЕ РАСТВОРЫ В ФАРМАЦИИ
THE IMPACT OF DEUTERIUM CONTENT IN WATER ON CELL CYCLE REGULATION AND GENE EXPRESSION-THE EFFECT OF DEUTERIUM DEPLETION ON THE SURVIVAL AND RECURRENCE OF CANCER PATIENTS
Somlyai G.
HYD LLC for Cancer Research and Drug Development, HYD Pharma Inc. Villanyi ut 97.
Budapest, 1118 Hungary
The pH shift of cytoplasm to alkaline after mitogen stimulation was considered already in the early 80's as a key step before cell division commences. Today, to create inhibitors of Na+/H+ exchanger (NHE), the predominant membrane transporter to regulate intracellular pH, is one of the most promising strategies to develop anticancer drugs. This concept is strongly supported by the fact that reversed pH gradient in cancer cells, the highly acidic extracellular pH are hallmarks of all malignancies. The data also suggest that NHE is sensitive to deuterium concentration, as recovery of intracellular pH after acidification was modified by altering deuterium level of the medium. In in vitro experiments, deuterium-depleted media (30-100 ppm D) inhibited but D-enriched media (300-600 ppm) stimulated growth rate of different cancer cell lines. To reveal the effect of D on the genes having important role in the cell cycle, expression of 237 cancer-related and 537 kinase genes was investigated by NanoString technology.
Gene expression in A549 lung cancer cells in media containing 40, 80, and 300 ppm D was compared to cells growing in media containing 150 ppm D. Interestingly, only 6 cancer-related and 1 kinase genes showed inhibition higher than 30%, while the expression of 123 cancer-related and 134 kinase genes was stimulated over 30%, respectively. An in vivo mice study revealed that deuterium-depleted water (DDW) inhibited the expression of genes having key role in tumor development after carcinogen exposure and on the long-term DDW inhibited tumor development. A retrospective analysis of human data confirmed that integration of deuterium depletion into conventional therapy drastically reduced the relapse rate, as out of 204 cancer patients, who started consuming DDW in remission, only 13 patients were lost during the 1,024 years of the cumulative follow-up time.
We suggest that the highly activated NHE discriminates between hydrogen and deuterium and prefers to transport the lighter isotope elevating the intracellular D/H ratio, which is the key regulator of metabolism and gene expression, as the consequence of the highly acidic extracellular pH. Properly working mitochondria produce deuterium-depleted metabolic water and are able to control cell growth by reducing the D/H ratio, but mitochondria in cancer cells are dysfunctional. Application of DDW can inhibit the growth of cancer cells, as the replacement of normal water with DDW will substitute for the function of damaged mitochondria.
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