Exogenous normal mammary epithelial mitochondria suppress glycolytic metabolism and glucose uptake of human breast cancer cells
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.
KeywordsBreast cancer Normal mitochondrial transplantation Real-time PCR Aerobic glycolysis Lactate
Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR)
Glucose transporter 1
Glucose transporter 3
Phosphoglycerate kinase 1
Triosephosphate isomerase 1
Lactate dehydrogenase A
Nicotinamide adenine dinucleotide
This research was supported by funds from The Sallie Astor Burdine and Delta State University Foundations, Baton Rouge, Louisiana.
Compliance with ethical standards
Conflict of interest
No conflicting financial interest exists.
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