Targeting cancer cells through antibiotics-induced mitochondrial dysfunction requires autophagy inhibition.
A significant part of current research studies utilizes various cellular models which imply specific antibiotics-containing media as well as antibiotics used for clonal selection or promoter de/activation. With the great success of developing such tools, mitochondria, once originated from bacteria, can be effectively targeted by antibiotics. For that reason, some studies propose antibiotics-targeting of mitochondria as part of anticancer therapy. Here, we have focused on the effects of various classes of antibiotics on mitochondria in cancer and non-cancer cells and demonlow mitochondrial membrane potential, reduced ATP production, altered morphology and lowered respiration rate which altogether suggested mitochondrial dysfunction (MDF). This was in parallel with increased level of reactive oxygen species (ROS) and decreased activity of mitochondrial respiration complexes. However, both survival and repopulation capacity of cancer cells was not significantly affected by the antibiotics, perhaps due to a glycolytic shift or activated autophagy. In turn, simultaneous inhibition of autophagy and treatment with antibiotics largely reduced tumorigenic properties of cancer cells suggesting potential strategy for anticancer therapy.
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Milan
M
Esner
Novosibirsk State University, Novosibirsk, Pirogova 2, 630090, Russia.
Dmitry
D
Graifer
Translational Research in Cancer Stem Cells, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
Matilde E
ME
Lleonart
Translational Research in Cancer Stem Cells, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Novosibirsk Institute of Molecular Biology and Biophysics, Novosibirsk, Russia; ICRC-FNUSA, International Clinical Research Center and St. Anne's University Hospital Brno, Czech Republic. Electronic address: lyakhovich@gmail.com.
Alex
A
Lyakhovich
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
D000900:Anti-Bacterial Agents; D045222:Electron Transport Chain Complex Proteins; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; C025946:3-methyladenine; D000255:Adenosine Triphosphate; D000225:Adenine
Antibiotics; Autophagy; Cancer; Mitochondria; Mitochondrial dysfunction; Mitophagy