Abstract 5420: Normal mammary epithelial mitochondria introduced into human breast cancer cells results in inhibition of proliferation and increased drug sensitivity of the MCF-7 breast cancer cell line.

Abstract

Abstract Warburg in the 1920s postulated that mitochondrial dysfunction alters metabolism in cancer. He observed in cancer cells aerobic glycolysis, which is the conversion of glucose to lactic acid in the presence of oxygen, the so called “Warburg effect” [1]. Mitochondrial dysfunction of cancer cells includes increased aerobic glycolysis, elevated levels of ROS, decreased apoptosis, and resistance to chemotherapeutic agents. We reported on the ultrastructural observations of mitochondria in human breast carcinoma cells [2]. There were three distinct groups: (1) mitochondria absent, (2) mitochondria present, (3) mitochondria present but sparse and abnormal. Tumors in the absent group were more anaplastic, aggressive, and resistant to treatment. We hypothesized that the introduction of normal mitochondria into cancer cells might restore mitochondrial function and inhibit cancer cell growth, and reverse chemoresistance. First we tested if mitochondria of normal mammary epithelial MCF-12A cells could enter into cultured human cancer cells. Then we determined if introducing normal mitochondria into cancer cells would inhibit proliferation. Finally we determined if addition of normal mitochondria increases the sensitivity of human breast cancer MCF-7 cells to chemotherapy. We found JC-1 stained mitochondria from normal mammary epithelial MCF-12A cells can enter into the cancer cell lines MCF-7, MDA-MB-231, and NCI/ADR-Res, but cannot enter normal MCF-12 A cells. The normal mitochondria from normal MCF-12 A cells suppressed the proliferation of MCF-7 and NCI/ADR-Res cells in a dose dependent pattern, but did not affect the proliferation of normal MCF-12A cells. The normal mitochondria from normal MCF-12A cells increased the sensitivity of human breast cancer MCF-7 cells to doxorubicin, Abraxane, and carboplatin. In conclusion the introduction of normal mammary mitochondria into human cancer cells inhibits cancer cell proliferation and increases the sensitivity of the MCF-7 human breast cancer cells to doxorubicin, Abraxane, and carboplatin. This phenomenon has never been reported, and the results support the role of mitochondrial dysfunction in cancer and suggest the possible use of targeted mitochondria as an adjunct to cancer therapeutics. Citation Format: Robert L. Elliott, Xian P. Jian, Jonathan F. Head. Normal mammary epithelial mitochondria introduced into human breast cancer cells results in inhibition of proliferation and increased drug sensitivity of the MCF-7 breast cancer cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5420. doi:10.1158/1538-7445.AM2013-5420