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Exogenous normal mammary epithelial mitochondria suppress glycolytic metabolism and glucose uptake of human breast cancer cells

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Abstract

We hypothesized that normal mitochondria inhibited cancer cell proliferation and increased drug sensitivity by the mechanism of suppression of cancer aerobic glycolysis. To demonstrate the mechanism, we used real-time PCR and glycolysis cell-based assay to measure gene expression of glycolytic enzymes and glucose transporters, and extracellular lactate production of human breast cancer cells. We found that isolated fluorescent probe-stained mitochondria of MCF-12A (human mammary epithelia) could enter into human breast cancer cell lines MCF-7, T47D, and MDA-MB-231, confirmed by fluorescent and confocal microscopy. Mitochondria from the untransformed human mammary epithelia increased drug sensitivity of MCF-7 cells to paclitaxel. Real-time PCR showed that exogenous normal mitochondria of MCF-12A suppressed gene expression of glycolytic enzymes, lactate dehydrogenase A, and glucose transporter 1 and 3 of MCF-7 and MDA-MB-231 cells. Glycolysis cell-based assay revealed that normal mitochondria significantly suppressed lactate production in culture media of MCF-7, T47D, and MDA-MB-231 cells. In conclusion, normal mitochondria suppress cancer proliferation and increase drug sensitivity by the mechanism of inhibition of cancer cell glycolysis and glucose uptake.

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Abbreviations

RT-qPCR:

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR)

OXPHOS:

Oxidative phosphorylation

ATP:

Adenosine triphosphate

JC-1:

5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide

SLC2A1:

Glucose transporter 1

SLC2A3:

Glucose transporter 3

ALDOC:

Aldolase A

ENO1:

Enolase 1

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GPI:

Glucose-6-phosphate isomerase

HK2:

Hexokinase

PFKM:

Phosphofructokinase-1

PGK1:

Phosphoglycerate kinase 1

PKM2:

Pyruvate kinase

TMI:

Triosephosphate isomerase 1

LDHA:

Lactate dehydrogenase A

NADH:

Nicotinamide adenine dinucleotide

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Acknowledgments

This research was supported by funds from The Sallie Astor Burdine and Delta State University Foundations, Baton Rouge, Louisiana.

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Correspondence to Xian-Peng Jiang.

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Jiang, XP., Elliott, R.L. & Head, J.F. Exogenous normal mammary epithelial mitochondria suppress glycolytic metabolism and glucose uptake of human breast cancer cells. Breast Cancer Res Treat 153, 519–529 (2015). https://doi.org/10.1007/s10549-015-3583-0

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  • DOI: https://doi.org/10.1007/s10549-015-3583-0

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