Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players

Autor: Min-Hee Kang, Jin-Hoi Kim, Muniyandi Jeyaraj, Sangiliyandi Gurunathan
Rok vydání: 2021
Předmět:
platinum nanoparticle
Serum
Lung Neoplasms
Metal Nanoparticles
Pharmaceutical Science
02 engineering and technology
Exosomes
01 natural sciences
chemistry.chemical_compound
International Journal of Nanomedicine
Drug Discovery
oxidative stress
Original Research
Aniline Compounds
Chemistry
General Medicine
021001 nanoscience & nanotechnology
Neoplasm Proteins
Cell biology
Gene Expression Regulation
Neoplastic

Sphingomyelin Phosphodiesterase
acetylcholinesterase activity
Acetylcholinesterase
cytotoxicity
0210 nano-technology
Ceramide
Cell Survival
Static Electricity
Biophysics
Nanoparticle tracking analysis
Adenocarcinoma of Lung
Bioengineering
Ceramides
010402 general chemistry
Benzylidene Compounds
Exosome
Biomaterials
exosome
Humans
Secretion
RNA
Messenger

Particle Size
Cell Proliferation
Platinum
A549 cell
neutral sphingomyelinase activity
Lutein
Organic Chemistry
Microvesicles
Acetylcysteine
0104 chemical sciences
Enzyme Activation
A549 Cells
Cancer cell
Biogenesis
Zdroj: International Journal of Nanomedicine
ISSN: 1178-2013
DOI: 10.2147/ijn.s291138
Popis: Sangiliyandi Gurunathan, Min-Hee Kang, Muniyandi Jeyaraj, Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaTel +82 2 450 3687Fax + 82 2 544 4645Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.krBackground: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549).Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function.Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.Keywords: exosome, platinum nanoparticle, cytotoxicity, oxidative stress, acetylcholinesterase activity, neutral sphingomyelinase activity
Databáze: OpenAIRE