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Multicellular Human Alveolar Model Composed of Epithelial Cells and Primary Immune Cells for Hazard Assessment
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Combination Effect of Silver Nanoparticles and Histone Deacetylases Inhibitor in Human Alveolar Basal Epithelial

Sangiliyandi Gurunathan1, Min-Hee Kang2, Jin-Hoi Kim3

  • 1Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. gsangiliyandi@yahoo.com.

Molecules (Basel, Switzerland)
|August 17, 2018
PubMed

Insights

This study shows that combining silver nanoparticles (AgNPs) with MS-275, a histone deacetylase inhibitor (HDACi), effectively triggers cancer cell death. This novel lung cancer treatment strategy induces apoptosis through the intrinsic pathway.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Lung cancer treatment faces challenges due to its aggressive nature.
  • Combination therapies with silver nanoparticles (AgNPs) and histone deacetylase inhibitors (HDACi) show promise but require mechanistic understanding.

Purpose of the Study:

  • To investigate the mechanism of combined AgNPs and HDACi (MS-275) therapy in lung cancer.
  • To evaluate the efficacy of AgNPs synthesized using wogonin in combination with MS-275 against A549 lung cancer cells.

Main Methods:

  • Synthesis and characterization of AgNPs using wogonin.
  • Assessment of AgNP toxicity on A549 cells.
  • Evaluation of combined AgNPs and MS-275 effects on apoptosis, reactive oxygen species (ROS), lactate dehydrogenase (LDH) release, TNFα secretion, mitochondrial function, and gene expression.

Main Results:

  • Synthesized AgNPs demonstrated dose- and size-dependent toxicity to A549 cells.
  • The combination of AgNPs and MS-275 significantly induced apoptosis via the mitochondrial-mediated intrinsic pathway.
  • Key indicators of apoptosis, including ROS generation, LDH leakage, TNFα secretion, caspase activation, and DNA fragmentation, were observed.

Conclusions:

  • The combination of AgNPs and MS-275 represents a promising therapeutic strategy for lung cancer.
  • This combination induces lung cancer cell death through the intrinsic apoptotic pathway.
  • Further research is warranted to advance this combination therapy towards clinical application.
Keywords:
DNA damageMS-275apoptosisautophagosomescombination therapycytotoxicityoxidative stresssilver nanoparticles

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