Despite the convincing empirical evidence that deuterium depleted water (DDW, 25-125 ppm deuterium) has anticancer effect, the molecular mechanism remains unclear. Here, redox proteomics investigation of the DDW action in A549 cells revealed an increased level of oxidative stress, whereas expression proteomics in combination with thermal profiling uncovered crucial role of mitochondrial proteins. In the proposed scenario, reversal of the normally positive deuterium gradient across the inner membrane leads to an increased export of protons from the matrix to intermembrane space and an increase in the mitochondrial membrane potential, enhancing the production of reactive oxygen species (ROS). The resulting oxidative stress leads to slower growth and can induce apoptosis. However, further deuterium depletion in ambient water triggers a feedback mechanism, which leads to restoration of the redox equilibrium and resumed growth. The DDW-induced oxidative stress, verified by traditional biochemical assays, may be helpful as an adjuvant to ROS-inducing anticancer therapy.
Keywords: Chemoproteomics; anticancer; cancer therapeutics; deuterium depleted water; oxidative stress; proteomics; quantification; redox disbalance; tandem mass spectrometry.
© 2019 Zhang et al.