Improvement in antiproliferative activity of Angelica gigas Nakai by solid dispersion formation via hot-melt extrusion and induction of cell cycle arrest and apoptosis in HeLa cells

Biosci Biotechnol Biochem. 2015;79(10):1635-43. doi: 10.1080/09168451.2015.1046363. Epub 2015 Jun 9.

Abstract

Angelica gigas Nakai (AGN) is one of the most popular herbal medicines and widely used as a functional food product. In this study, AGN was firstly processed by a low-temperature turbo mill and a hot melting extruder to reduce particle size and form solid dispersion (SD). Anticancer activity against HeLa cells was then examined. AGN-SD based on Soluplus was formed via hot-melt extrusion (HME) and showed the strongest cytotoxic effect on HeLa cells. In addition, the possible mechanism of cell death induced by AGN-SD on HeLa cells was also investigated. AGN-SD decreased cell viability, induced apoptosis, increased the production of reactive oxygen species, regulated the expression of Bcl-2 and Bax, and induced G2/M phase arrest in HeLa cells. This study suggested that AGN-SD based on Soluplus and the method to improve antiproliferative effect by SD formation via HME may be suitable for application in the pharmaceutical industry.

Keywords: apoptosis; cell cycle; cytotoxic effect; hot-melt extrusion; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelica / chemistry*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Freezing
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • Polyethylene Glycols / chemistry
  • Polyvinyls / chemistry
  • Pressure
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • Plant Extracts
  • Polyvinyls
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Polyethylene Glycols