Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells
Sangiliyandi Gurunathan, Jin Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaCorrespondence: Jin Hoi Kim, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea, Tel +82 2 450 3687, Fax +82 2 544 4645, Emai...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-11-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/graphene-oxide-enhances-biogenesis-and-release-of-exosomes-in-human-ov-peer-reviewed-fulltext-article-IJN |
| _version_ | 1797963680514572288 |
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| author | Gurunathan S Kim JH |
| author_facet | Gurunathan S Kim JH |
| author_sort | Gurunathan S |
| collection | DOAJ |
| description | Sangiliyandi Gurunathan, Jin Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaCorrespondence: Jin Hoi Kim, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea, Tel +82 2 450 3687, Fax +82 2 544 4645, Email jhkim541@konkuk.ac.krBackground: Exosomes, which are nanovesicles secreted by almost all the cells, mediate intercellular communication and are involved in various physiological and pathological processes. We aimed to investigate the effects of graphene oxide (GO) on the biogenesis and release of exosomes in human ovarian cancer (SKOV3) cells.Methods: Exosomes were isolated using ultracentrifugation and ExoQuick and characterized by various analytical techniques. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.Results: Graphene oxide (10– 50 μg/mL), cisplatin (2– 10 μg/mL), and C6-ceramide (5– 25 μM) inhibited the cell viability, proliferation, and cytotoxicity in a dose-dependent manner. We observed that graphene oxide (GO), cisplatin (CIS), and C6-Ceramide (C6-Cer) stimulated acetylcholine esterase and neutral sphingomyelinase activity, total exosome protein concentration, and exosome counts associated with increased level of apoptosis, oxidative stress and endoplasmic reticulum stress. In contrast, GW4869 treatment inhibits biogenesis and release of exosomes. We observed that the human ovarian cancer cells secreted exosomes with typical cup-shaped morphology and surface protein biomarkers. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in GO-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from GO-treated SKOV3 cells than in those isolated from control cells. SKOV3 cells pre-treated with N-acetylcysteine or GW4869 displayed a significant reduction in GO-induced exosome biogenesis and release. Furthermore, endocytic inhibitors decrease exosome biogenesis and release by impairing endocytic pathways.Conclusion: This study identifies GO as a potential tool for targeting the exosome pathway and stimulating exosome biogenesis and release. We believe that the knowledge acquired in this study can be potentially extended to other exosome-dominated pathologies and model systems. Furthermore, these nanoparticles can provide a promising means to enhance exosome production in SKOV3 cells.Keywords: graphene, exosome, oxidative stress, endoplasmic reticulum stress, endocytic pathways, human ovarian cancer cells |
| first_indexed | 2024-04-11T01:33:09Z |
| format | Article |
| id | doaj.art-f2eb2af88c294fc99b5fe1ec4945bb89 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-11T01:33:09Z |
| publishDate | 2022-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-f2eb2af88c294fc99b5fe1ec4945bb892023-01-03T09:29:44ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-11-01Volume 175697573179933Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer CellsGurunathan SKim JHSangiliyandi Gurunathan, Jin Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaCorrespondence: Jin Hoi Kim, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea, Tel +82 2 450 3687, Fax +82 2 544 4645, Email jhkim541@konkuk.ac.krBackground: Exosomes, which are nanovesicles secreted by almost all the cells, mediate intercellular communication and are involved in various physiological and pathological processes. We aimed to investigate the effects of graphene oxide (GO) on the biogenesis and release of exosomes in human ovarian cancer (SKOV3) cells.Methods: Exosomes were isolated using ultracentrifugation and ExoQuick and characterized by various analytical techniques. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.Results: Graphene oxide (10– 50 μg/mL), cisplatin (2– 10 μg/mL), and C6-ceramide (5– 25 μM) inhibited the cell viability, proliferation, and cytotoxicity in a dose-dependent manner. We observed that graphene oxide (GO), cisplatin (CIS), and C6-Ceramide (C6-Cer) stimulated acetylcholine esterase and neutral sphingomyelinase activity, total exosome protein concentration, and exosome counts associated with increased level of apoptosis, oxidative stress and endoplasmic reticulum stress. In contrast, GW4869 treatment inhibits biogenesis and release of exosomes. We observed that the human ovarian cancer cells secreted exosomes with typical cup-shaped morphology and surface protein biomarkers. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in GO-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from GO-treated SKOV3 cells than in those isolated from control cells. SKOV3 cells pre-treated with N-acetylcysteine or GW4869 displayed a significant reduction in GO-induced exosome biogenesis and release. Furthermore, endocytic inhibitors decrease exosome biogenesis and release by impairing endocytic pathways.Conclusion: This study identifies GO as a potential tool for targeting the exosome pathway and stimulating exosome biogenesis and release. We believe that the knowledge acquired in this study can be potentially extended to other exosome-dominated pathologies and model systems. Furthermore, these nanoparticles can provide a promising means to enhance exosome production in SKOV3 cells.Keywords: graphene, exosome, oxidative stress, endoplasmic reticulum stress, endocytic pathways, human ovarian cancer cellshttps://www.dovepress.com/graphene-oxide-enhances-biogenesis-and-release-of-exosomes-in-human-ov-peer-reviewed-fulltext-article-IJNgrapheneexosomeoxidative stressendoplasmic reticulum stressendocytic pathwayshuman ovarian cancer cells |
| spellingShingle | Gurunathan S Kim JH Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells International Journal of Nanomedicine graphene exosome oxidative stress endoplasmic reticulum stress endocytic pathways human ovarian cancer cells |
| title | Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells |
| title_full | Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells |
| title_fullStr | Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells |
| title_full_unstemmed | Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells |
| title_short | Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells |
| title_sort | graphene oxide enhances biogenesis and release of exosomes in human ovarian cancer cells |
| topic | graphene exosome oxidative stress endoplasmic reticulum stress endocytic pathways human ovarian cancer cells |
| url | https://www.dovepress.com/graphene-oxide-enhances-biogenesis-and-release-of-exosomes-in-human-ov-peer-reviewed-fulltext-article-IJN |
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