Ray wrote many articles about the redox state of cancer cells and their overall reductive state. In addition, he mentioned he crucial role reduced glutathione (GSH) plays in protecting cancer cells from the immune system (T-cells) and the toxic reactive oxygen species (ROS) cancer cells produce due to their excessive oxidation of fatty acids. Studies as far back as the 1950s demonstrated that GSH depletion strongly inhibits tumor growth and/or makes the cancer cells much more responsive to traditional therapy, especially chemo and radiation. One of the main mechanism’s of action for aspirin, acetoacetate, and various quinones (e.g. emodin, vitamin K, CoQ10, tetracyclines, methylene blue, etc) is depletion of GSH and conversion into the oxidized version GSSG. Medicine views GSH depletion as bad, but this dogma does not stand up to scrutiny. While depletion of the so-called “total glutathione pool” is arguably not healthy, the substances mentioned above do not deplete it, but rather convert GSH into GSSG. Thus, the total glutathione pool remains largely unchanged, but the GSH/GSSG ratio drops and that changes the redox state of the cell away from reduction towards oxidation.
One of the required precursors for glutathione synthesis is cysteine. Ray wrote about the role of cysteine as a reductant and thyroid inhibitor (as well as the similar role of methionine, tryptophan, ammonia, histamine, serotonin, etc), so cysteine seems to have a direct negative effect of its own, but its role in cancer is probably more related to its role as glutathione precursor. Depletion of cysteine has been shown to inhibit GSH synthesis and would thus also be expected to be therapeutic for cancer. Since cysteine is a non-essential amino acid, dietary restriction may not have a significant enough impact on cancer (though, it would still be beneficial for metabolism). A direct interference with endogenous cysteine availability is needed for cancer therapy. Rather than target L-cysteine directly, the study below simply gave the animals with cancer a supplement of the mirror (chiral) image of L-cysteine known as D-cysteine. The latter has the same molecular mass and structure as L-cysteine, but cannot be used by the body for GSH synthesis. In effect, this amounts of (L)cysteine depletion, and this approach was also found to inhibit tumor growth. Finally, this approach seems to target exclusively cancer cells and leaves normal cells unharmed, demonstrating that neither cysteine nor glutathione are as crucial for good health as many medical articles would have us believe.
https://www.nature.com/articles/s42255-025-01339-1
“…Many cancer treatments harm healthy tissue along with tumors, often leading to serious side effects. To reduce this collateral damage, researchers are searching for therapies that act only on cancer cells. An international research team led by the Universities of Geneva (UNIGE) and Marburg has identified an unusual approach involving a “mirror” version of the amino acid cysteine. This sulfur-containing molecule sharply slows the growth of certain cancers while leaving healthy cells unaffected. Because it is taken up mainly by specific cancer cells, the compound disrupts essential functions such as cellular respiration and DNA production. In experiments with mice, this strategy significantly reduced the growth of aggressive breast tumors, suggesting a promising and highly targeted treatment avenue. The results are reported in Nature Metabolism.”
“…Amino acids are the basic building blocks of proteins and are essential for life. All organisms rely on the same set of 20 amino acids, which exist in two structural forms known as L (levorotatory) and D (dextrorotatory). These forms are mirror images of each other, comparable to left and right hands. Although they share the same chemical makeup, their three-dimensional arrangement differs. Human cells almost exclusively use the L forms to build proteins, while D forms play little role in normal biology. The research team, led by Jean-Claude Martinou, Honorary Professor in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science, examined how different amino acids influence cancer cell behavior. Their experiments revealed that the D form of cysteine (D-Cys), which contains a sulfur atom, strongly suppresses the growth of certain cancer cells in laboratory conditions. Notably, healthy cells were unaffected, highlighting a striking level of selectivity.”
