Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 17, Issue 8, Pages 2021-2033Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.59581
Keywords
mitochondrial transplantation therapy; melanoma; cell cycle arrest; apoptosis
Categories
Funding
- National Natural Science Foundation of China [82073830]
- Chongqing Key Program of Basic Research and Advanced Exploration Project [cstc2019jcyjzdxmX0035]
- Chongqing Innovation Project for Returnees from Overseas Scholars in 2018 [cx2018086]
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Mitochondrial transplantation therapy has been actively researched as a treatment for mitochondria-associated diseases, including malignant melanoma. This study investigated the signal mechanism and gender differences in the anti-tumor activity of healthy mitochondria. The results showed that intact mitochondria significantly inhibited tumor cell proliferation and showed anti-tumor effects in melanoma-bearing mice, with female mitochondria demonstrating greater efficiency and a possible stronger mitochondria-nuclear communication than male mitochondria.
Today mitochondria are considered much more than a energy plant in cells. Mitochondrial transplantation therapy has been an active research area for treating mitochondria-associated diseases from animal studies to clinical trials. However, the specific mechanism involved in the anti-tumor activity of healthy mitochondria remain to be characterized. Here we investigate the signal mechanism and gender difference of mitochondrial transplantation therapy against malignant melanoma. In the study, we administrated intact mitochondria extracted from mouse livers respectively to the mice bearing malignantly subcutaneous and metastatic melanoma, and identified the signal mechanism responsible for the mitochondrial treatment through transcriptomic analysis. Meanwhile, the efficiency of female mitochondria and male mitochondria was compared in the cultured melanoma cells and transplanted melanoma in mice. The results suggested that the mitochondria significantly inhibited the tumor cell proliferation in vitro through cell cycle arrest and induction of cell apoptosis. In the melanoma-bearing mice, the mitochondria retard the tumor growth and lung migration, and the transcriptomic analysis indicated that general chromosome silencing was strongly associated with the mitochondria against melanoma after the mitochondrial transplantation on the metastasis melanoma. Moreover, the anti-tumor activity of mitochondria from female animals was more efficient in comparison to the males, and the female mitochondria could probably induce more persuasive mitochondria-nuclear communication than the mitochondria from male mice. The study identifies the anti-tumor mechanism of the mitochondrial transplantation therapy, and provides a novel insight into the effect of mitochondria from different gender.
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