Chemical toxicology is a rapidly evolving field that targets various types of cancer cells. The strategies are based on glucose metabolism, mechanisms of cell death, bioactivation and enzyme induction. Cancer cells heavily rely on abnormal glycolysis, which involves overexpressed hexokinase II (HKII). This catalyzes the first step of glycolysis, therefore, therapeutically targeting HKII. This allows it to change critical metabolic pathway in cancer cells. Abnormal glycolysis coverts large amount ATP to promote growth, so, another attractive target for tumor therapy is apoptosis induced by glucose deprivation. Cancer cells not only consume glucose, but also require glutamine, another major nutrient. Specifically, glutamine which is precursor of intermediates of Krebs cycle. As a result, glutamine starvation may also be a future strategy that researchers could use for cancer therapy.
Even though glucose metabolism is one of the major cancer therapy targets in chemical toxicology, some reactive metabolite byproduct of glycolysis has become a hot topic for treating cancers, such as methylglyoxal will reacts with glutathione (GSH) in non-enzymatical condition to form lactoylglutathione (LGSH). This could accumulate to a high concentration level of tumor cells and promote tumor growth. This allows the argument to be made that methylglyoxal inhibits the detoxification of reactive metabolites is, as it suppresses the growth of cancer cell.
Key words: glucose metabolism, mechanisms of cell death, bioactivation, enzyme induction, Warburg effect
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