Silver nanoparticles defeat p53-positive and p53-negative osteosarcoma cells by triggering mitochondrial stress and apoptosis.
Loss of function of the tumour suppressor p53 observed frequently in human cancers challenges the drug-induced apoptotic elimination of cancer cells from the body. This phenomenon is a major concern and provides much of the impetus for current attempts to develop a new generation of anticancer drugs capable of provoking apoptosis in a p53-independent manner. Since silver nanoparticles (AgNPs) possess unique cytotoxic features, we examined, whether their activity could be exploited to kill tumour suppressor-deficient cancer cells. Therefore, we investigated the effects of AgNPs on osteosarcoma cells of different p53 genetic backgrounds. As particle diameters might influence the molecular mechanisms leading to AgNP-induced cell death we applied 5 nm and 35 nm sized citrate-coated AgNPs. We found that both sized AgNPs targeted mitochondria and induced apoptosis in wild-type p53-containing U2Os and p53-deficient Saos-2 cells. According to our findings AgNPs are able to kill osteosarcoma cells independently from their actual p53 status and induce p53-independent cancer cell apoptosis. This feature renders AgNPs attractive candidates for novel chemotherapeutic approaches.
Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
Dávid
D
Kovács
Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
Nóra
N
Igaz
Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
Csilla
C
Keskeny
Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1. H-6720, Szeged, Hungary.
Péter
P
Bélteky
Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1. H-6720, Szeged, Hungary.
Tímea
T
Tóth
Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9. Szeged, H-6720, Hungary.
Renáta
R
Gáspár
Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1. H-6720, Szeged, Hungary.
Dániel
D
Madarász
Department of Pathology, University of Szeged, Állomás utca. 2. H-6720, Szeged, Hungary.
Zsolt
Z
Rázga
Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1. H-6720, Szeged, Hungary.|MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, H-6720, Szeged, Hungary.
Zoltán
Z
Kónya
Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.|Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Temesvári krt. 62, H-6726, Szeged, Hungary.
Imre M
IM
Boros
Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
Mónika
M
Kiricsi
D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019343:Citric Acid / Q000737:chemistry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D015398:Signal Transduction / Q000187:drug effects; D012834:Silver / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D019343:Citric Acid; D012834:Silver