TY - JOUR

T1 - Targeting cancer cells through antibiotics-induced mitochondrial dysfunction requires autophagy inhibition

AU - Esner, Milan

AU - Graifer, Dmitry

AU - Lleonart, Matilde E.

AU - Lyakhovich, Alex

N1 - Copyright © 2016. Published by Elsevier Ireland Ltd.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Autophagy

KW - Cancer

KW - Mitochondria

KW - Mitochondrial dysfunction

KW - Mitophagy

KW - Mitochondrial Degradation/drug effects

KW - Humans

KW - Autophagy/drug effects

KW - Electron Transport Chain Complex Proteins/metabolism

KW - Anti-Bacterial Agents/pharmacology

KW - Antineoplastic Combined Chemotherapy Protocols/pharmacology

KW - Microtubule-Associated Proteins/genetics

KW - Transfection

KW - Time Factors

KW - Mitochondria/drug effects

KW - Female

KW - Cell Proliferation/drug effects

KW - Breast Neoplasms/drug therapy

KW - Reactive Oxygen Species/metabolism

KW - Adenosine Triphosphate/metabolism

KW - Signal Transduction/drug effects

KW - Membrane Potential, Mitochondrial/drug effects

KW - Drug Synergism

KW - Energy Metabolism/drug effects

KW - Cell Line, Tumor

KW - Adenine/analogs & derivatives

KW - FANCONI-ANEMIA CELLS

KW - MANNER

KW - RESISTANCE

UR - http://www.scopus.com/inward/record.url?scp=84994052462&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2016.09.023

DO - 10.1016/j.canlet.2016.09.023

M3 - Article

C2 - 27693455

AN - SCOPUS:84994052462

VL - 384

SP - 60

EP - 69

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

ER -