Nejvíce citovaný článek - PubMed ID 26697128
Bypassing Mechanisms of Mitochondria-Mediated Cancer Stem Cells Resistance to Chemo- and Radiotherapy
Nanodiamonds represent an attractive potential carrier for anticancer drugs. The main advantages of nanodiamond particles with respect to medical applications are their high compatibility with non-cancerous cells, feasible surface decoration with therapeutic and cancer-cell targeting molecules, and their relatively low manufacturing cost. Additionally, nanodiamond carriers significantly increase treatment efficacy of the loaded drug, so anticancer drugs execute more effectively at a lower dose. Subsequently, lower drug dose results in less extensive side effects. The carriers decorated with a targeting molecule accumulate primarily in the tumor tissue, and those nanodiamond particles impair efflux of the drug from cancer cells. Therapeutic approaches considering nanodiamond carriers were already tested in vitro, as well as in vivo. Now, researchers focus particularly on the possible side effects of nanodiamond carriers applied systemically in vivo. The behavior of nanodiamond carriers depends heavily on their surface coatings, so each therapeutic complex must be evaluated separately. Generally, it seems that site-specific application of nanodiamond carriers is a rather safe therapeutic approach, but intravenous application needs further study. The benefits of nanodiamond carriers are remarkable and represent a potent approach to overcome the drug resistance of many cancers.
- Klíčová slova
- Nanodiamond, cancer therapy, drug carrier, drug resistance, nanoparticles,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cancer cells are known to reprogram their metabolism to adapt to adverse conditions dictated by tumor growth and microenvironment. A subtype of cancer cells with stem-like properties, known as cancer stem cells (CSC), is thought to be responsible for tumor recurrence. In this study, we demonstrated that CSC and chemoresistant cells derived from triple negative breast cancer cells display an enrichment of up- and downregulated proteins from metabolic pathways that suggests their dependence on mitochondria for survival. Here, we selected antibiotics, in particular - linezolid, inhibiting translation of mitoribosomes and inducing mitochondrial dysfunction. We provided the first in vivo evidence demonstrating that linezolid suppressed tumor growth rate, accompanied by increased autophagy. In addition, our results revealed that bactericidal antibiotics used in combination with autophagy blocker decrease tumor growth. This study puts mitochondria in a spotlight for cancer therapy and places antibiotics as effective agents for eliminating CSC and resistant cells.
- Klíčová slova
- Antibiotics, Autophagy, Breast Cancer, Cancer Biology, Cancer Stem Cells, Chemoresistance, Clinical Proteomics, Mitochondria, Mitochondria Function or Biology, NMR, NMR-metabolomic, Stem Cells,
- MeSH
- chemorezistence * účinky léků MeSH
- lidé MeSH
- linezolid aplikace a dávkování farmakologie MeSH
- metabolické sítě a dráhy * účinky léků MeSH
- mitochondrie účinky léků metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky účinky léků metabolismus MeSH
- nádorové mikroprostředí účinky léků MeSH
- proliferace buněk účinky léků MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- transplantace nádorů MeSH
- triple-negativní karcinom prsu farmakoterapie metabolismus patologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- linezolid MeSH