Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production
Received 11 February 2018
Accepted for publication 28 March 2018
Published 31 May 2018 Volume 2018:13 Pages 3235—3250
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Thomas Webster
Ana Carolina Martínez-Torres, Diana G Zarate-Triviño, Helen Yarimet Lorenzo-Anota, Andrea Ávila-Ávila, Carolina Rodríguez-Abrego, Cristina Rodríguez-Padilla
Laboratory of Immunology and Virology, Faculty of Biological Sciences, Autonomous University of Nuevo Leon, Monterrey, Mexico
Background: Nanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and detection of diseases is a growing trend in this field. As cancer represents a serious health problem around the world, AuNPs are studied as potential drugs or drug carriers for anticancer agents. Recent studies show that AuNPs stabilized with chitosan (CH) possess interesting biological activities, including potential antitumor effects that could be selective to cancer cells.
Materials and methods: In this study, we synthesized sodium citrate-AuNPs and CH-capped AuNPs of 3–10 nm, and analyzed their cytotoxicity in cervical (HeLa) and breast (MCF-7) cancer cells, and in peripheral blood mononuclear cells (PBMCs). Then, we evaluated the clonogenic potential, cell cycle, nuclear alterations, caspase dependence, and reactive oxygen species (ROS) production in HeLa and MCF-7 cells after chitosan gold nanoparticles (CH-AuNPs) exposure.
Results: Our data showed that CH-AuNPs are cytotoxic in a dose-dependent manner in the cancer cell lines tested, while they induce low cytotoxicity in PBMCs. Sodium citrate gold nanoparticles did not show cytotoxic effects. In both HeLa and MCF-7 cell lines, CH-AuNPs inhibit clonogenic potential without inducing cell cycle arrest or nuclear alterations. The cell death mechanism is specific for the type of cancer cell line tested, as it depends on caspase activation in HeLa cells, whereas it is caspase independent in MCF-7 cells. In all cases, ROS production is mandatory for cell death induction by CH-AuNPs, as ROS inhibition with N-acetyl cysteine inhibits cell death.
Conclusion: Our results show that CH-AuNPs are selective for HeLa and MCF-7 cancer cells, rather than normal PBMCs, and that ROS production seems to be a conserved feature of the cell death mechanism induced by CH-AuNPs. These results improve the knowledge of CH-AuNPs and open the way to the design of new pharmacological strategies using these agents against cancer.
Keywords: AuNPs, cancer, PBMC, nuclear alterations, cell cycle, ROS
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