Analysis of the Warburg Effect and Lactate Dehydrogenase Inhibition in SK-BR3, MDA-MB-453, DLD-1, and HT-29 Cancer Cells

Student Author Information

John Tomkinson, Lynchburg CollegeFollow

Access Type

Open Access

Entry Number

43

Start Date

4-5-2017 12:00 PM

End Date

4-5-2017 1:00 PM

Department

Biomedical Science

Abstract

Due to the Warburg effect, cancer cells metabolize preferentially through lactic acid fermentation, as opposed to aerobic respiration which is more typical of cells in the body. Lactic acid fermentation is catalyzed through the key enzyme lactase dehydrogenase (LDH). Therefore, targeting lactase dehydrogenase may prove an indirect method of targeting cancer cells. Sodium oxamate is therefore being used to inhibit LDH to study potential effectiveness for inhibiting the metabolism and proliferation of cancer cells. In order to compare the efficacy of this inhibition across different cancer cell lines, breast cancer cell lines SK-BR3 and MDA-MB-453 will be examined and compared to colon epithelial cell lines DLD-1 and HT-29. Differences in chromosomal mutations and patient gender will also be considered. Cell proliferation and ATP production will be examined using XTT assays to measure cell count and luciferase assays to measure ATP production with and without sodium oxamate treatment. If LDH inhibition by sodium oxamate results in a reduction of proliferation and metabolic activity, it suggests a potential clinical application; differences in cell lines may prompt further lines of inquiry or suggest areas of ideal application.

Faculty Mentor(s)

Dr. Jablonski

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Apr 5th, 12:00 PM Apr 5th, 1:00 PM

Analysis of the Warburg Effect and Lactate Dehydrogenase Inhibition in SK-BR3, MDA-MB-453, DLD-1, and HT-29 Cancer Cells

Due to the Warburg effect, cancer cells metabolize preferentially through lactic acid fermentation, as opposed to aerobic respiration which is more typical of cells in the body. Lactic acid fermentation is catalyzed through the key enzyme lactase dehydrogenase (LDH). Therefore, targeting lactase dehydrogenase may prove an indirect method of targeting cancer cells. Sodium oxamate is therefore being used to inhibit LDH to study potential effectiveness for inhibiting the metabolism and proliferation of cancer cells. In order to compare the efficacy of this inhibition across different cancer cell lines, breast cancer cell lines SK-BR3 and MDA-MB-453 will be examined and compared to colon epithelial cell lines DLD-1 and HT-29. Differences in chromosomal mutations and patient gender will also be considered. Cell proliferation and ATP production will be examined using XTT assays to measure cell count and luciferase assays to measure ATP production with and without sodium oxamate treatment. If LDH inhibition by sodium oxamate results in a reduction of proliferation and metabolic activity, it suggests a potential clinical application; differences in cell lines may prompt further lines of inquiry or suggest areas of ideal application.