Sensitization of MDA-MBA231 breast cancer cell to docetaxel by myricetin loaded into biocompatible lipid nanoparticles via sub-G1 cell cycle arrest mechanism

Naunyn Schmiedebergs Arch Pharmacol. 2020 Jan;393(1):1-11. doi: 10.1007/s00210-019-01692-5. Epub 2019 Aug 2.

Abstract

The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation behavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer.

Keywords: Apoptosis; Docetaxol; Myricetin; Nanostructured lipid carrier (NLC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel / administration & dosage*
  • Docetaxel / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Fatty Acids / administration & dosage
  • Fatty Acids / chemistry
  • Flavonoids / administration & dosage*
  • Flavonoids / chemistry
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Fatty Acids
  • Flavonoids
  • Docetaxel
  • glyceryl behenate
  • myricetin