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Faculty Mentor

Hemachand Tummala

Abstract

The third leading cause of cancer deaths in the U.S. is colon cancer. The major disadvantage of cancer chemotherapy is its non-selective toxicity to healthy cells at the therapeutic doses. A possible target selective for cancer cells is their dependence on glycolysis for cellular energy. 2-deoxyglucose (2-DG) is a glycolytic inhibitor that has been shown to be safe in both animals and humans. The molecular mechanisms for the anticancer effect of 2-DG cannot be explained solely by its glycolytic inhibition. In this manuscript we studied the effect of 2-DG on colon cancer cells and its possible molecular mechanism. Colon cancer cells are more susceptible to 2-DG treatment than other cancerous and non-cancerous cell lines tested. The colon cancer cells tested are SW620, SW480 and GC3/C1. In cell cycle analysis studied using propidium iodide staining of DNA followed by flow-cytometry, 2-DG induced cell cycle arrest at G0/G1 phase in SW 620 cells. 2-DG also modified the expression of various cell cycle proteins such as p21, p53, and cyclins as measured through Western Blotting. In addition to cell cycle arrest, 2-DG also induced apoptosis through activation of Caspase 3. Complementing 5-Fluorouracil (5- FU) treatment of colon cancer cells with 2-DG significantly enhanced the efficiency of 5- FU treatment up to 3.5 fold. This study showed a new molecular mechanisms for 2-DG that could be used to design novel combination therapies with other known chemotherapeutic agents for colon cancer. The addition of a well-tolerated molecule like 2- DG increases the efficiency of 5-FU, thus reducing the patient’s cumulative exposure to 5- FU. This may lead to fewer dose dependent side effects and better patient outcomes.

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