Abstract A89: Glycolytic cancer cell metabolism suppressed by transplantation of exogenous normal mitochondria into human breast cancer cells

Abstract

Abstract Most cancer cells switch metabolism from mitochondria-based glucose oxidation to cytoplasmic glycolysis even under normoxia (the Warburg effect). The effect promotes tumorigenesis, cancer growth, invasion and drug resistance. We hypothesize that introduction of normal mitochondria into cancer cells might suppress the Warburg effect. Normal human (MCF-12A) and mouse (EpH4-Ev) mammary epithelia, and human breast cancer (MCF-7) and mouse mammary adenocarcinoma (4T1) cell lines were used in this study. We found that isolated fluorescent probe-stained mitochondria of MCF-12A or EpH4-Ev could enter into cancer cells when co-cultured with MCF-7 or 4T1 cells respectively, confirmed by fluorescent and confocal microscopy. The mitochondria from MCF-12A cells inhibited the proliferation of breast cancer MCF-7 cells in a dose dependent pattern and increased drug sensitivity of MCF-7 cells to doxorubicin, paclitaxel and carboplatin. Real time qPCR showed that exogenous normal mitochondria suppressed the gene expression of 11 glycolytic enzymes, and glucose transporter 1 and 3 of MCF-7 cells. These results suggest that normal mitochondria suppress cancer proliferation and increase drug sensitivity by the mechanism of inhibition of cancer cell glycolysis and glucose consumption. Isolated mitochondria have remained viable in culture for over three weeks and still actively entered cancer cells and inhibited cancer proliferation. In mouse model bearing the 4T1 mammary adenocarcinoma, isolated MitoTracker orange dye-stained mitochondria of EpH4-Ev, when directly injected into tumor mass, entered into 4T1 cancer cells in 24 hours. Therefore, normal mitochondrial transfer could be a cell-based therapy for cancer and other mitochondrial disorders. Citation Format: Robert L. Elliott, Xian-Peng Jiang, Jonathan F. Head. Glycolytic cancer cell metabolism suppressed by transplantation of exogenous normal mitochondria into human breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A89.