An ellagitannin-loaded CS-PEG decorated PLGA nano-prototype promotes cell cycle arrest in colorectal cancer cells

Cell Biochem Biophys. 2023 Jun;81(2):313-323. doi: 10.1007/s12013-023-01132-5. Epub 2023 Apr 17.

Abstract

Colorectal cancer is associated with significant morbidity and mortality worldwide. Egypt, as a developing country, has a high-rise incidence of cancer. The current study objective was to investigate the antitumor influences of ellagitannin-loaded CS-PEG-decorated PLGA nano-prototypes against human colorectal cancer cell lines (HCT 116 as well as Caco-2) in vitro. Doxorubicin (DOX), punicalin (PN), and punicalagin (PNG)-encapsulated chitosan-polyethylene glycol-decorated PLGA (PLGA-CS-PEG) nanoparticles (NPs) were described. The cytotoxicity of each preparation was evaluated using MTT assays in HCT 116 as well as Caco-2 cells during G0, G1, S, and G2 cell cycle phases. Cell cycle-related gene expression and protein levels were measured after treatment. Reactive oxygen species (ROS) levels were also measured. Both PN and PNG PLGA-CS-PEG NPs induce colon cancer cell death with cell cycle arrest in the G1 phase in vitro. Caco-2 cells were more sensitive to the nano-therapy than HCT 116 cells. Upon treatment, the ratio of Bax to Bcl-2 expression was increased following nano-therapy, with increased levels of Cas-3 and decreased expression of Bcl-2, PI3k, and NF-ĸB compared to control. The nitric oxide level (NO), a marker of ROS, was increased following nano-therapy compared to control. In conclusion, ROS-mediated cell cycle arrest can be induced by PN as well as PNG nano-therapy in cell lines of colorectal cancer.

Keywords: Chemotherapy; Colon cancer cells; Ellagitannins; PLGA-CS-PEG nanoparticles.

MeSH terms

  • Caco-2 Cells
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Colorectal Neoplasms*
  • Drug Carriers
  • Humans
  • Hydrolyzable Tannins / pharmacology
  • Nanoparticles*
  • Polyethylene Glycols
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Reactive Oxygen Species

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Drug Carriers
  • Hydrolyzable Tannins
  • Reactive Oxygen Species
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols