Document Type : Review
HYD LLC for Cancer Research and Drug Development, Fürj u. 2, Budapest 1124, Hungary
Behnam Javaheri--Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran.,Petro Parsian Pharmed Inc. Tehran, Iran.
The two stable isotopes of hydrogen, protium (1H) and deuterium (2H) differ in their physicochemical nature. Deuterium-depleted water (DDW) significantly inhibited the growth rate of different tumor cell lines in culture media and xenotransplanted MDA-MB-231, MCF-7 human breast adenocarcinomas and PC-3 human prostate tumors in vivo. The apoptosis-triggering effect of DDW was demonstrated both in vitro and in vivo. The anti-cancer effect of D-depletion was also confirmed in a double-blind, randomized, 4-month-long, human phase II clinical trial on prostate cancer. D-depletion, as an adjuvant, caused 3-7 fold increases of median survival time (MST) in lung cancer, two-fold in advanced breast cancer and it also effectively prevented recurrences of early stage breast cancer. It is suggested that the cell cycle regulating system is able to recognize the changes in the 2H/1H ratio. Two key events takes place in the cell at the same time: the binding of growth hormone to the receptor activates the H+-transport system, which preferentially eliminates H+, resulting in an increased 2H/1H ratio, which is essential to start cell division; the properly working mitochondria, the terminal complex of mitochondrial electron transport chain reducing molecular oxygen to DDW, which reduces the 2H/1H ratio and inhibits the cell growth. The balance between the activated H+-transport system and the DDW producing mitochondria which determine the 2H/1H ratio in the cells is proposed as the key mechanism to regulate cell growth.