Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase

@article{Fiorillo2021BedaquilineAF,
  title={Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase},
  author={Marco Fiorillo and Cristian Scatena and Antonio Giuseppe Naccarato and Federica Sotgia and Michael P Lisanti},
  journal={Cell Death and Differentiation},
  year={2021},
  volume={28},
  pages={2797 - 2817}
}
Here, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important… Expand

Figures from this paper

High ATP Production Fuels Cancer Drug Resistance and Metastasis: Implications for Mitochondrial ATP Depletion Therapy
Recently, we presented evidence that high mitochondrial ATP production is a new therapeutic target for cancer treatment. Using ATP as a biomarker, we isolated the “metabolically fittest” cancer cellsExpand
Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and Metabolic Plasticity of Cancer Cells During Metastasis
The role of metabolism in tumor growth and chemoresistance has received considerable attention, however, the contribution of mitochondrial bioenergetics in migration, invasion, and metastasis isExpand

References

SHOWING 1-10 OF 37 REFERENCES
Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs)
TLDR
It is shown that bedaquiline has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs), and it is demonstrated that bedquiline treatment of MCF7 breast cancer cells inhibits mitochondrial oxygen-consumption, as well as glycolysis, but induces oxidative stress. Expand
Deferiprone (DFP) Targets Cancer Stem Cell (CSC) Propagation by Inhibiting Mitochondrial Metabolism and Inducing ROS Production
TLDR
It is proposed that DFP is a new candidate therapeutic for drug repurposing and for Phase II clinical trials aimed at eradicating CSCs. Expand
First-in-class candidate therapeutics that target mitochondria and effectively prevent cancer cell metastasis: mitoriboscins and TPP compounds
TLDR
These studies provide the necessary proof-of-concept, and in vivo functional evidence, that mitochondrial inhibitors can successfully and selectively target the biological process of cancer cell metastasis and envision that mitochondrial inhibitor could be employed to develop new treatment protocols, for clinically providing metastasis prophylaxis, to help prevent poor clinical outcomes in cancer patients. Expand
Bedaquiline inhibits the yeast and human mitochondrial ATP synthases
TLDR
Bedaquiline (BDQ, Sirturo), approved to treat multi-drug-resistant tuberculosis, inhibits the yeast and human mitochondrial ATP synthases in addition to its intended target, the Mycobacterium tuberculosis ATP synthase. Expand
A mitochondrial based oncology platform for targeting cancer stem cells (CSCs): MITO-ONC-RX
TLDR
This general approach, using FDA-approved antibiotics to target mitochondria, was effective in killing CSCs originating from many different cancer types, including DCIS, breast (ER(+) and ER(-)), prostate, ovarian, lung and pancreatic cancers, as well as melanoma and glioblastoma, among others. Expand
Mitochondria as new therapeutic targets for eradicating cancer stem cells: Quantitative proteomics and functional validation via MCT1/2 inhibition
TLDR
The results indicate that inhibition of MCT1/2 function effectively reduces mammosphere formation, with an IC-50 of ~1 μM, in both ER-positive and ER-negative breast cancer cell lines. Expand
Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.
TLDR
It is shown that high expression of the mRNA species encoding HMGR is associated with poor clinical outcome in breast cancer patients, providing a potential companion diagnostic for BMF-directed personalized therapy. Expand
High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant
TLDR
Increased mitochondrial mass in a sub-population of breast cancer cells confers a stem-like phenotype and chemo-resistance, and the current findings have important clinical implications for over-coming drug resistance, by therapeutically targeting the mito-high CSC population. Expand
Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease
TLDR
It is proposed to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types, and these drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Expand
A Myristoyl Amide Derivative of Doxycycline Potently Targets Cancer Stem Cells (CSCs) and Prevents Spontaneous Metastasis, Without Retaining Antibiotic Activity
TLDR
Current studies provide proof-of-principle, that existing FDA-approved drugs can be further modified and optimized, to successfully target the anchorage-independent growth of CSCs and to prevent the process of spontaneous tumor cell metastasis. Expand
...
1
2
3
4
...