Selenium Nanoparticles Synthesized Using Pseudomonas stutzeri (MH191156) Show Antiproliferative and Anti-angiogenic Activity Against Cervical Cancer Cells

Int J Nanomedicine. 2020 Jun 23:15:4523-4540. doi: 10.2147/IJN.S247426. eCollection 2020.

Abstract

Purpose: Selenium nanoparticles (SeNP) have several applications in the field of biotechnology, including their use as anti-cancer drugs. The purpose of the present study is to analyze the efficacy of green synthesis on the preparation of SeNP and its effect on their anti-cancer properties.

Methods: A bacterial strain isolated from a freshwater source was shown to efficiently synthesize SeNP with potential therapeutic properties. The quality and stability of the NP were studied by scanning electron microscopy, X-ray diffraction, zeta-potential and FTIR analysis. A cost-effective medium formulation from biowaste having 6% banana peel extract enriched with 0.25 mM tryptophan was used to synthesize the NP. The NP after optimization was used to analyze their anti-tumor and anti-angiogenic activity. For this purpose, first, the cytotoxicity of the NP against cancer cells was analyzed by MTT assay and then chorioallantoic membrane assay was performed to assess anti-angiogenic activity. Further, cell migration assay and clonogenic inhibition assay were performed to test the anti-tumor properties of SeNP. To assess the cytotoxicity of SeNP on healthy RBC, hemolysis assay was performed.

Results: The strain identified as Pseudomonas stutzeri (MH191156) produced phenazine carboxylic acid, which aids the conversion of Se oxyanions to reduced NP state, resulting in particles in the size range of 75 nm to 200 nm with improved stability and quality of SeNP, as observed by zeta (ξ) potential of the particles which was found to be -46.2 mV. Cytotoxicity of the SeNP was observed even at low concentrations such as 5 µg/mL against cervical cancer cell line, ie, HeLa cells. Further, neovascularization was inhibited by upto 30 % in CAMs of eggs coinoculated with SeNp when compared with untreated controls, indicating significant anti-angiogenic activity of SeNP. The NP also inhibited the invasiveness of HeLa cells as observed by decreased cell migration and clonogenic proliferation. These observations indicate significant anti-tumor and anti-angiogenic activity of the SeNP in cervical cancer cells.

Conclusion: P. stutzeri (MH191156) is an efficient source of Se NP production with potential anti-angiogenic and anti-tumor properties, particularly against cervical cancer cells.

Keywords: MH191156; Pseudomonas stutzeri; anti-angiogenic activity; cell migration; cervical cancer cells; clonal proliferation; selenium nanoparticles.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Death / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chick Embryo
  • Costs and Cost Analysis
  • Female
  • HeLa Cells
  • Hemolysis / drug effects
  • Humans
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Phenazines / chemistry
  • Pseudomonas stutzeri / metabolism*
  • Reproducibility of Results
  • Selenium / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Uterine Cervical Neoplasms / blood supply
  • Uterine Cervical Neoplasms / pathology
  • X-Ray Diffraction

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Phenazines
  • 1-phenazinecarboxylic acid
  • Selenium