Journal
ONCOTARGETS AND THERAPY
Volume 13, Issue -, Pages 5241-5255Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S238143
Keywords
mitochondrial transplantation; animal model of breast cancer; Pep-1; MDA-MB-231; tumor growth; mitochondrial fusion
Categories
Funding
- National Science Council [MOST 1062314-B-371-004, MOST 107-2314-B-371-005]
- Changhua Christian Hospital [107-CCH-MST-012]
Ask authors/readers for more resources
Background: The transfer of whole mitochondria has been demonstrated to be beneficial for treating breast cancer because it induces apoptosis and drug sensitivity; however, in vivo evidence of this benefit remains scant. The present study compared the transplantation of mitochondria with instinctive (Mito) and membrane-fused morphologies induced by Pep-1 conjugation (P-Mito) using a mouse model of triple-negative breast cancers. Materials and Methods: Mice with advanced severe immunodeficiency received orthotopic implantation of MDA-MB-231 human breast cancer cells followed by transplants of 5-bromo-2'-deoxyuridine (BrdU)-labeled Mito or P-Mito (200 mu g [10 mu g/mu L]) through intratumoral injection at multiple points once a week for 4 weeks. Results: After 1 month of consecutive treatment, 8.2% and 14.2% of the BrdU-labeled mitochondria were preserved in tumors of the Mito and P-Mito groups, respectively. Both Pep-1 and P-Mito treatments reduced tumor weight (21.7% +/- 2.43% vs 40.6% +/- 2.28%) and led to marked inhibition of Ki67 staining and angiogenesis. However, only the P-Mito group exhibited obvious necrosis and DNA fragmentation accompanied by an altered tumor microenvironment, which included reduced oxidative stress and size of cancer-associated fibroblast populations and enhanced immune cell infiltration. Transmission electron microscopy images further revealed an elongated network of perinuclear mitochondria fused with a few peripheral mitochondria in the nonnecrotic area in the P-Mito group as well as increases in mitochondrial fusion proteins and parkin compared with mitochondrial fission proteins. Conclusion: In this study, the results of mitochondrial transplantation emphasized that the facilitation of mitochondrial fusion is a critical regulator in breast cancer therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available