Bongkrekic Acid as a Warburg Effect Modulator in Long-term Estradiol-deprived MCF-7 Breast Cancer Cells

Background/Aim: An in vitro cell model of long-term estrogen-deprived MCF-7 (LTED) cells has been utilized to analyze the re-growth mechanisms of breast cancers treated with blockers for estrogen receptor alpha (ER alpha) signaling. Bongkrekic acid (BKA) is a natural toxin isolated from coconut tempeh contaminated with the bacterium Burkholderia cocovenans. Materials and Methods: LTED cells, MCF-7 cells and MDA-MB-231 cells were employed in the study. After treatment with BKA (chemically synthesized; purity: >98%), several biochemical analyses were carried out. Results: LTED cells were categorized into an oxidative phenotype. When LTED cells were treated with BKA, lactate dehydrogenase A (LDHA)/pyruvate dehydrogenase kinase 4 (PDK4) were downregulated, thereby prompting the aggressive use of glucose via mitochondrial oxidative phosphorylation and induction of cell death responses. These effects of BKA were not observed in the other breast cancer cells analyzed. Conclusion: We suggest the potential of BKA as an experimental tool for the analysis of cancer biology in LTED cells.