ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles

Int J Nanomedicine. 2021 Mar 9:16:1993-2011. doi: 10.2147/IJN.S277014. eCollection 2021.

Abstract

Background: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape.

Methods: In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy.

Results: Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1-5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death.

Conclusion: These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.

Keywords: anti-cancer therapy; apoptosis; autophagy; gold nanoparticles; gold nanopeanuts; nanotechnology; ovarian cancer.

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / drug effects
  • Arachis
  • Autophagy* / drug effects
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Gold / chemistry*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / toxicity
  • Metal Nanoparticles / ultrastructure
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • Gold

Grants and funding

This work was financially supported by grants from the National Science Centre, Poland (UMO-2018/31/B/NZ6/02476 to RB), and Medical University of Bialystok (SUB/1/DN/20/003/1122 to EP). Part of the study was conducted with the use of equipment purchased by the Medical University of Białystok as part of the RPOWP 2007–2013 funding, Priority I, Axis 1.1, contract No. UDA- RPPD.01.01.00-20-001/15-00 dated June 26, 2015. This work was supported by the program of the Minister of Science and Higher Education under the name “Regional Initiative of Excellence in 2019–2022“, project number: 024/RID/2018/19, financing amount: 11.999.000,00 PLN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.