In 2009, Dr. Ko and Peterson uncovered an important key to the metabolic reprogramming of the mitochondria in cancer cells. In cancer cells, the embryonic form of Hexokinase, called hexokinase II is formed which is not present in normal cells. It is attached to the outer membrane of the pores of the mitochondrial, called the voltage dependent anion channel (VDZC). This is the first enzyme in the metabolism of glucose, and its location on the mitochondrial outer membrane allow for massive utilization of glucose to feed the cancer.
3 bromopyruvate causes cancer cell death by separation of HK II from the outer mitochondrial membrane of the cancer. It is a small nontoxic molecule that induces apoptosis and cell death in cancer cells while sparing normal cells. It provides a promising cancer treatment.
It is an alkylating agent, and it has a high degree of specificity for its anticancer activity. It can alkylate and inactivate metabolic enzymes, which are upregulated in cancer cells.
In addition, 3 BP causes overexpression of reactive oxygen species along with glutathione depletion which is important in cancer cell apoptosis and death.
It also causes a rise in intracellular acidosis and the tumor by inhibition of MCT 1 expression which is important in the cell death of cancer cells. It also targets complex 1 and 2 of the electron transport chain which contributes to ATP depletion and cancer cell death.
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