Date of Award

2015

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Gordon MacGregor

Committee Member

Eric Mendenhall

Committee Member

Debra M. Moriarity

Subject(s)

Cancer--Genetic aspects., Cancer cells., Hyperglycemia.

Abstract

Many cancer cells rely predominately on glycolysis for their energy production, even in the presence of oxygen. They proceed further and reduce the glycolysis product pyruvate to lactate, by means of fermentation, for continued ATP production. This phenomenon is called the Warburg effect, and is associated with an upregulation of glycolysis and increased lactate production. A persistent increase in glycolysis and ATP turnover leads to an intracellular proton accumulation, which could eventually lead to cell damage and death by cytosolic acidification. However, cancer cells avoid acidification and maintain an appropriate intracellular pH by employing monocarboxylate transporters for the coupled export of protons with lactate. Preventing the export of protons with a monocarboxylate transporter inhibitor, results in a decrease in cancer cell growth due to cell cycle arrest. In hyperglycemic conditions, the effect of the monocarboxylate transporter was amplified, resulting in an even larger decrease in the rate of cell division and cell number. Thus, targeting cancer cells using their abnormal physiology has provided a means to decrease their growth, and weaken them, potentially making them more amenable to treatment with chemotherapeutic agents.

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