Stabilization of Zataria essential oil with pectin-based nanoemulsion for enhanced cytotoxicity in monolayer and spheroid drug-resistant breast cancer cell cultures and deciphering its binding mode with gDNA

Int J Biol Macromol. 2020 Dec 1:164:3645-3655. doi: 10.1016/j.ijbiomac.2020.08.084. Epub 2020 Aug 12.

Abstract

Efficacy of chemotherapy is limited by the resistance of cancer cells. Phytochemicals especially Essential Oils (EOs) provide an alternative mode of cancer therapy. However, EOs utilization is restricted because of low bioavailability, and high degradation. Nanoemulsification is a method developed to overcome these obstacles. Accordingly, Citrus-Pectin nanoemulsion of Zataria Essential Oil (CP/ZEONE) was prepared to evaluate the anticancer activity and the mechanisms responsible for the caused cytotoxicity. Physical properties and FTIR spectra of CP/ZEONE were characterized. CP/ZEONE progressively improves the suppression of viability of drug-resistant MCF-7, MDA-MB-231 breast cancer cells, and spheroids. It triggers apoptosis by increasing Reactive Oxygen Species (ROS), mitochondrial membrane potential (MMP) loss, DNA damage, G2 and S-phase arrest in MDA-MB-231 cells and spheroids respectively. Additionally, spectroscopy techniques revealed the interaction of CP/ZEONE with DNA via the formation of a groove binding/partial intercalative complex. Thus, ZEO-loaded CP Nano-particles can be further explored as a promising antiproliferative and therapeutic candidate against cancer.

Keywords: Apoptosis; Breast cancer; DNA damage/interaction; Mitochondria; Nanoemulsion; Spheroid.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / chemistry
  • DNA / drug effects
  • DNA Damage / drug effects
  • Emulsions / chemistry
  • Emulsions / pharmacology
  • Female
  • Humans
  • Lamiaceae / chemistry*
  • Membrane Potential, Mitochondrial / drug effects
  • Nanocomposites / chemistry
  • Oils, Volatile / chemistry
  • Oils, Volatile / pharmacology*
  • Pectins / chemistry*
  • Pectins / pharmacology
  • Reactive Oxygen Species / chemistry
  • Spheroids, Cellular / chemistry
  • Spheroids, Cellular / drug effects

Substances

  • Antineoplastic Agents
  • Emulsions
  • Oils, Volatile
  • Reactive Oxygen Species
  • citrus pectin
  • Pectins
  • DNA