title: Exogenous normal mammary epithelial mitochondria suppress glycolytic metabolism and glucose uptake of human breast cancer cells.
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.
authors.affiliation: EEH Breast Cancer Research and Treatment Center, 11441 Industriplex Blvd, Suite 190, Baton Rouge, LA, 70809, USA. jiang2003x@yahoo.com.
authors.forename: Xian-Peng
authors.initials: XP
authors.lastname: Jiang
authors.affiliation: EEH Breast Cancer Research and Treatment Center, 11441 Industriplex Blvd, Suite 190, Baton Rouge, LA, 70809, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Elliott
authors.affiliation: EEH Breast Cancer Research and Treatment Center, 11441 Industriplex Blvd, Suite 190, Baton Rouge, LA, 70809, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Head
mesh_terms: D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D005947:Glucose
keywords: Aerobic glycolysis; Breast cancer; Lactate; Normal mitochondrial transplantation; Real-time PCR