Co-delivery with nano-quercetin enhances doxorubicin-mediated cytotoxicity against MCF-7 cells

Mol Biol Rep. 2016 Feb;43(2):99-105. doi: 10.1007/s11033-016-3942-x. Epub 2016 Jan 9.

Abstract

Quercetin, the plant-derived phenolic compounds, plays a pivotal role in controlling hemostasis, by having potent antioxidant and free-radical scavenging properties. This flavonoid in combination with chemotherapeutic drugs improves the efficacy of these agents in induction of apoptosis in cancer cells. This study investigated the role of nano-quercetin (phytosome) in doxorubicin-induced apoptosis. Nanoparticles were characterized for particle size, zeta potential, scanning electron microscopy (SEM) and differential scanning calorimetric assessments. Anti-proliferative effect of formulations was evaluated by MTT assay. mRNA expression levels of target genes were measured by real time RT-PCR. The mean size of nanoparticles was 85 ± 2 nm with nearly narrow size distribution which was confirmed by SEM analysis. Our results showed that co-treatment of MCF-7 breast cancer cells with nano-quercetin and doxorubicin increased the percentage of apoptosis from 40.11 ± 7.72-58 ± 7.13 (p < 0.05). Furthermore, mRNA expression levels for downstream genes including NQO1 and MRP1 showed a marked decrease (p < 0.05). Taken together, our results suggest that phytosome technology can elevate the efficacy of chemotherapeutics by increasing the permeability of tumor cells to chemical agents. Our findings introduce a novel phytosome-dependent strategy to improve delivery of doxorubicin to the breast cancerous tissues.

Keywords: Chemoresistance; MCF-7; Phytosome; Quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Membrane Permeability / drug effects
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Quercetin / chemistry
  • Quercetin / pharmacology*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Doxorubicin
  • Quercetin
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • multidrug resistance-associated protein 1