Inhibition of tumor growth by replacing glutathione with N-acetyl-L-cysteine

Abstract

There have been several attempts to prevent the tumor growth and the resulting death. However, almost none of the developed methods designed to inhibit tumor growth gives a satisfactorily result without deleterious side effects. Some of the existing methods employed on prevention of tumor growth and invasion target the metabolic differences between normal and tumor cells. The most pronounced metabolic differences between normal and tumor cells appear to be in the energy generating pathways. The energy generating pathways in normal cells are inter-regulated and the most developed pathway controls the activity of the least developed pathway. Cancer cells do not respond to these regulations and as a result energy generating pathways start to operate independently. Among the energy generating pathways, the least developed or the most primitive pathway is the non-phosphorylating glycolysis. The increased activity of this pathway has been suggested to provide the cells with sufficient mitotic activity. It has been suggested that in non-phosphorylating glycolysis, glucose is broken down to lactate in a manner that requires glutathione. Here, I hypothesize that manipulation of intracellular glutathione concentrations as protecting the cells form oxidative stress may efficiently inhibit tumor growth. Glutathione is a soluble antioxidant and its concentration is high in prenatal tissue and in cancer cells. Though its primary function seems to combat against oxidant injury and toxic xenobiotics, glutathione is implicated in many other different cellular processes including cell proliferation and DNA and RNA synthesis. Another function of glutathione relevant to the subject is its involvement in detoxification of methylglyoxal, a compound that is generated at high concentrations in rapidly proliferating cells possessing an inhibitory activity on cell proliferation. Therefore, inhibition of intracellular glutathione concentration may negatively impact the tumor cell growth by at least three ways. The first is through inhibition of non-phosphorylating glycolysis that provides mitotic energy for cells. The second is through the inhibition of methylglyoxal metabolism and the third is through the redox regulation of DNA and RNA synthesis.