Breast Cancer Research and Treatment

, Volume 136, Issue 2, pp 347–354 | Cite as

Mitochondria organelle transplantation: introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity

  • R. L. ElliottEmail author
  • X. P. Jiang
  • J. F. Head


Mitochondrial dysfunction of cancer cells includes increased aerobic glycolysis, elevated levels of ROS, decreased apoptosis, and resistance to chemotherapeutic agents. We hypothesized that the introduction of normal mitochondria into cancer cells might restore mitochondrial function and inhibit cancer cell growth, and reverse chemoresistance. First, in the present study, we tested if mitochondria of immortalized, untransformed mammary epithelial MCF-12A cells could enter into human cancer cell lines. Second, if introducing normal mitochondria into cancer cells would inhibit proliferation. And third, would the addition of normal mitochondria increase the sensitivity of human breast cancer MCF-7 cells to chemotherapy. We found that JC-1-stained mitochondria of immortalized, untransformed mammary epithelial MCF-12A cells can enter into the cancer cell lines MCF-7, MDA-MB-231, and NCI/ADR-Res, but cannot enter immortalized, untransformed MCF-12A cells. The normal mitochondria from immortalized, untransformed MCF-12A cells suppressed the proliferation of MCF-7 and NCI/ADR-Res cells in a dose-dependent pattern, but did not affect the proliferation of immortalized, untransformed MCF-12A cells. The normal mitochondria from immortalized, untransformed 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 breast cancer cells inhibits cancer cell proliferation and increases the sensitivity of the MCF-7 human breast cancer cell line to doxorubicin, Abraxane, and carboplatin. These results support the role of mitochondrial dysfunction in cancer and suggest the possible use of targeted mitochondria for cancer therapeutics.


Mitochondrial dysfunction Aerobic glycolysis Apoptosis Reactive oxygen species Chemoresistance 



Reactive oxygen species


Mitochondrial DNA


Succinate dehydrogenase


Hypoxia-inducible factor


Prolyl hydroxylase


Vascular endothelial growth factor


Adenosine triphosphate


Propaptotic ligand of Bcl-2 protein


Multidomain proapoptotic Bcl-2 protein


Proliferator-activated receptor-γ coactivator


Peroxisome proliferator-activated receptor



We also want to thank Lisa Allen for her assistance in preparing this manuscript and illustrations. Without her help the task would have been almost impossible.

Conflict of interest



  1. 1.
    Warburg O, Posener K, Negelein E (1924) Ueber den stoffwechsel der tumoren. Biochem Z 152:319–344Google Scholar
  2. 2.
    Warburg O, Wind F, Negelein E (1927) In metabolism of tumours. J Gen Physiol 8(6):519–530PubMedCrossRefGoogle Scholar
  3. 3.
    Hruszkewycz AM, Bergtold DS (1988) Oxygen radicals, lipid peroxidation and DNA damage in mitochondria. Basic Life Sci 49:449–456PubMedGoogle Scholar
  4. 4.
    Hruszkewycz AM (1992) Lipid peroxidation and mtDNA degeneration. A hypothesis. Mutat Res 275:243–248PubMedCrossRefGoogle Scholar
  5. 5.
    Richter C, Park JW, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 85:6465–6467PubMedCrossRefGoogle Scholar
  6. 6.
    Kroemer G (2006) Mitochondria in cancer. Oncogene 25:4630–4632PubMedCrossRefGoogle Scholar
  7. 7.
    Cuezva JM, Krajewska M, de Heredia ML et al (2002) The bioenergetic signature of cancer: a marker of tumor progression. Cancer Res 62:6674–6681PubMedGoogle Scholar
  8. 8.
    Carew JS, Huang P (2002) Mitochondrial defects in cancer. Mol Cancer 1:9PubMedCrossRefGoogle Scholar
  9. 9.
    Rossignol R, Gilkerson R, Aggeler R et al (2004) Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 64:985–993PubMedCrossRefGoogle Scholar
  10. 10.
    Petros JA, Baumann AK, Ruiz-Pesini E et al (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102:719–724PubMedCrossRefGoogle Scholar
  11. 11.
    Shidara Y, Yamagata K, Kanamori T et al (2005) Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res 65:1655–1663PubMedCrossRefGoogle Scholar
  12. 12.
    Gottlieb E, Tomlinson IP (2005) Mitochondrial tumor suppressors: a genetic and biochemical update. Nat Rev Cancer 5:857–866PubMedCrossRefGoogle Scholar
  13. 13.
    Elliott RL, Barnett BG (2011) Ultrastructural observations of mitochondria in human breast carcinoma cells. Microsc Microanal 1752:194–195CrossRefGoogle Scholar
  14. 14.
    Rieder H, Decker K (1984) Phagocytosis of hepatocytes mitochondria by rat Kupffer cells in vitro. Hoppe Seylers Z Physiol Chem 365(2):175–184PubMedCrossRefGoogle Scholar
  15. 15.
    Shi J, Irwin MH, Pinker CA (2008) Mitochondria transfer into fibroblasts: liposome-mediated transfer of labeled mitochondria into cultured cells. Ethn Dis 18:SI43–SI44Google Scholar
  16. 16.
    Pinkert CA, Irwin MH, Johnson LW et al (1997) Mitochondria transfer into mouse ova by microinjection. Transgenic Res 6:379–383PubMedCrossRefGoogle Scholar
  17. 17.
    Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159PubMedCrossRefGoogle Scholar
  18. 18.
    Xu RH, Pelicano H, Zhou Y et al (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621PubMedCrossRefGoogle Scholar
  19. 19.
    Gogvadze V, Orrenius S, Zhivotovsky B (2009) Mitochondria as targets for chemotherapy. Apoptosis 14:624–640PubMedCrossRefGoogle Scholar
  20. 20.
    Skildum A, Dornfeld K, Wallace K (2011) Mitochondrial amplification selectively increases doxorubicin sensitivity in breast cancer cells with acquired antiestrogen resistance. Breast Cancer Res Treat 129:785–797PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Elliott-Barnett-Head Breast Cancer Research and Treatment CenterBaton RougeUSA

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