Warburg Effect On Leukemia

University

Shawnee State University

Major

Biomedical Sciences/ Biology

Student Type

Undergraduate Student

Presentation Types

Oral Presentation (Live)

Keywords:

Leukemia, Warburg Effect, Cancer, Treatment

Abstract

Acute myeloid leukemia (AML) is a deadly cancer of the bone marrow and blood. Rapid proliferation leads to overcrowding of immature cancer cells, called blasts. AML cells survive through the Warburg Effect, a form of metabolic reprogramming in which cancer cells bypass efficient mitochondrial respiration in favor of rapid aerobic glycolysis. By converting the majority of glucose into lactate even when oxygen is abundant, AML cells can undergo rapid proliferation. In this study, we investigated the therapeutic potential of Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, to reverse this glycolytic dependency in the HL-60 AML cell line. By activating the pyruvate dehydrogenase complex, DCA forces pyruvate into the mitochondria, restoring oxidative phosphorylation and increasing reactive oxygen species (ROS) production. Data from MTT metabolic assays and direct-count kill curves have demonstrated a dose-dependent response in cell viability. A Western blot was also performed to determine whether CDK2, a vital cell cycle checkpoint protein, was downregulated upon DCA addition with inconclusive results.

Human and Animal Subjects

no

IRB or IACUC Approval

no

Faculty Mentor Name

Jennifer Napper

Faculty Mentor Title

Professor of Biology

Faculty Mentor Department

Natural Sciences

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Warburg Effect On Leukemia

Acute myeloid leukemia (AML) is a deadly cancer of the bone marrow and blood. Rapid proliferation leads to overcrowding of immature cancer cells, called blasts. AML cells survive through the Warburg Effect, a form of metabolic reprogramming in which cancer cells bypass efficient mitochondrial respiration in favor of rapid aerobic glycolysis. By converting the majority of glucose into lactate even when oxygen is abundant, AML cells can undergo rapid proliferation. In this study, we investigated the therapeutic potential of Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, to reverse this glycolytic dependency in the HL-60 AML cell line. By activating the pyruvate dehydrogenase complex, DCA forces pyruvate into the mitochondria, restoring oxidative phosphorylation and increasing reactive oxygen species (ROS) production. Data from MTT metabolic assays and direct-count kill curves have demonstrated a dose-dependent response in cell viability. A Western blot was also performed to determine whether CDK2, a vital cell cycle checkpoint protein, was downregulated upon DCA addition with inconclusive results.