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Oncotarget. 2015 Jan 20;6(2):662-78.

Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers.

Author information

1
Department of Oncologic Sciences, University of South Alabama Mitchell Cancer Institute, Mobile, AL 36604, USA.
2
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
3
Department of Oncologic Sciences, University of South Alabama Mitchell Cancer Institute, Mobile, AL 36604, USA.Department of Oncologic Research, University Hospital and Clinics, Lafayette General Health, Lafayette, LA 70503, USA.

Abstract

Metabolism is an important differentiating feature of cancer cells. Lactate dehydrogenases (LDH) A/B are metabolically important proteins and are involved in the critical step of inter-conversion of lactate to pyruvate. Panepoxydone (PP), a natural NF-kB inhibitor, significantly reduces the oxygen consumption and lactate production of MCF-7 and triple negative (MDA-MB-231, MDA-MB-468 and MDA-MB-453) breast cancer cells. We further observed that PP inhibited mitochondrial membrane potential and the ATP synthesis using flow cytometry. PP also up-regulated LDH-B and down-regulated LDH-A expression levels in all breast cancer cells to similar levels observed in HMEC cells. Over-expression of LDH-B in cancer cell lines leads to enhanced apoptosis, mitochondrial damage, and reduced cell migration. Analyzing the patient data set GDS4069 available on the GEO website, we observed 100% of non TNBC and 60% of TNBC patients had less LDH-B expression than LDH-A expression levels. Herein we report a new term called Glycolytic index, a novel method to calculate utilization of oxidative phosphorylation in breast cancer cells through measuring the ratio of the LDH-B to LDH-A. Furthermore, inhibitors of NF-kB could serve as a therapeutic agent for targeting metabolism and for the treatment of triple negative breast cancer.

PMID:
25575825
PMCID:
PMC4359247
DOI:
10.18632/oncotarget.2689
[Indexed for MEDLINE]
Free PMC Article

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