A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line

Anticancer Agents Med Chem. 2022;22(2):390-394. doi: 10.2174/1871520621666210308095712.

Abstract

Background: Hydroxytyrosol is one of the phenolic compounds of olive oil and can induce anticancer effects on colorectal cancer cells.

Objective: The aim of the present study was to evaluate the free hydroxytyrosol and nano-capsulated hydroxytyrosol effects on the cell cycle arrest in HT-29 colorectal cancer cell line.

Methods: The nano-capsulated hydroxytyrosol was synthesized in poly lactide-co-glycolide-co-polyacrylic acid (PLGA-PAA) copolymer. MTT assay was performed to evaluate the anti-proliferative and anti-tumor effects of the free hydroxytyrosol and nano-capsulated hydroxytyrosol. Finally, the relative expression of CDKN1A, CDKN1B, and CCND1 genes was evaluated in control and treated colorectal cancer cells by using Real-Time PCR.

Results: The obtained results from the MTT assay showed that the cytotoxic effects of the nano-capsulated hydroxytyrosol on the colorectal cancer cell line (IC50= 6PPM) were significantly more than free hydroxytyrosol (IC50= 12PPM) after 72h. Also, nano-capsulated hydroxytyrosol showed more significant effects on the upregulation of CDKN1A and CDKN1B genes and down-regulation of the CCND1 gene in colorectal cancer cells.

Conclusion: In conclusion, the present study showed that hydroxytyrosol led to the death of colorectal cancer cells through cell cycle arrest. Also, the PLGA-PAA copolymer dramatically caused to increase the cytotoxic effects of the hydroxytyrosol on the colorectal cancer cells.

Keywords: CCND1; CDKN1A; CDKN1B; Colorectal cancer; HT-29; PLGA-PAA copolymer; hydroxytyrosol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry
  • Acrylic Resins / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Capsules
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HT29 Cells
  • Humans
  • Nanoparticles / chemistry
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / chemistry
  • Phenylethyl Alcohol / pharmacology
  • Polyesters / chemistry
  • Polyesters / pharmacology*
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Acrylic Resins
  • Antineoplastic Agents
  • CCND1 protein, human
  • CDKN1A protein, human
  • CDKN1B protein, human
  • Capsules
  • Cyclin-Dependent Kinase Inhibitor p21
  • Polyesters
  • 3,4-dihydroxyphenylethanol
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Polyglycolic Acid
  • poly(lactide)
  • carbopol 940
  • Phenylethyl Alcohol