title: A novel biologically active acid stable liposomal formulation of docosahexaenoic acid in human breast cancer cell lines.
abstract: OBJECTIVE
  The risk of breast cancer can be influenced by certain dietary components, such as the amount and type of dietary fatty acids ingested. Docosahexaenoic acid (DHA), a component of fish oil, is known to suppress rat mammary carcinogenesis, reduce cell growth and induce apoptosis in human breast cancer cell lines. The purpose of this study was to develop a novel nanoliposomal formulation that would encapsulate a concentrated amount of DHA and utilize lipids that could protect DHA from pH fluctuations and oxidation.
  
  
  METHODS
  We developed an acid stable liposome formulation of DHA by utilizing ether and phytanyl lipids similar in structure to those found in Archaea, known to endure high acidity and temperature; we compared its biological activities with free DHA in human breast cancer cells.
  
  
  RESULTS
  The mean size of the liposomal DHA was 137 ± 12 nm with a slightly negative charge; the encapsulation efficiency of DHA in the liposomes as determined by LC-MS/MS ranged from 60 to 80%; our formulation is resistant to oxidation and stable over a range of pH (1.0-7.4) at 37 °C for a duration of two hours. In MCF-7 cells, liposomal DHA (IC50 38.8 μM) significantly reduced cell viability more effectively than free DHA (IC50 72.5 μM, p = 0.0017). In MDA-MB-231 cells, liposomal DHA was also marginally more effective. Liposomal DHA was more effective than free DHA in inducing apoptosis in both cell lines. It altered proteins involved in cell growth, cell cycle, and apoptosis more effectively than free DHA in both cell lines; it up-regulated p21 and cleaved PARP, while P-AKT and P-S6 were down-regulated.
  
  
  CONCLUSIONS
  We developed a novel biologically active acid stable liposomal DHA as a potentially useful formulation for breast cancer prevention.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Skibinski
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Arunangshu
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manni
authors.affiliation: NanoSTAR Institute, Department of Pharmacology, The University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Kester
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. Electronic address: kee2@psu.edu.
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D061986:MCF-7 Cells; D010084:Oxidation-Reduction
chemical_list: D016588:Anticarcinogenic Agents; D005395:Fish Oils; D008081:Liposomes; D004281:Docosahexaenoic Acids
keywords: Cancer prevention; Human breast cancer cell lines; Liposomal DHA