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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
Review

Abstract

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.

Keywords

Mitochondrial dysfunction Aerobic glycolysis Apoptosis Reactive oxygen species Chemoresistance 

Abbreviations

ROS

Reactive oxygen species

MtDNA

Mitochondrial DNA

SDH

Succinate dehydrogenase

HIF

Hypoxia-inducible factor

PHD

Prolyl hydroxylase

VEGF

Vascular endothelial growth factor

ATP

Adenosine triphosphate

BAD

Propaptotic ligand of Bcl-2 protein

BAX

Multidomain proapoptotic Bcl-2 protein

PGC-1α

Proliferator-activated receptor-γ coactivator

PPAR-γ

Peroxisome proliferator-activated receptor

Notes

Acknowledgments

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

None.

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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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