Trans-vaccenic acid inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via a mitochondrial-mediated apoptosis pathway

Lipids Health Dis. 2019 Feb 9;18(1):46. doi: 10.1186/s12944-019-0993-8.

Abstract

Background: Intake of trans fatty acids (TFAs) from partially hydrogenated vegetable oil is associated with a variety of adverse outcomes, but little is known about the health effects of ruminant trans fats. Trans-vaccenic acid (TVA) is a naturally occurring TFA found in the fat of ruminants and in human dairy products. The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells.

Methods: A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. Apoptosis was measured using flow cytometry. Western blotting was used to detect the protein expression levels of factors associated with Bcl-2-family protein signaling and Akt signaling.

Results: TVA significantly inhibited cell proliferation in a dose-dependent manner. Mechanistic investigation demonstrated that TVA significantly decreased p-Akt levels and Bad phosphorylation on Ser-136 and Ser-112. More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA.

Conclusion: TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. The combined use of TVA and Mcl-1 inhibitors offers a potential advantage for nasopharyngeal cancer treatment.

Keywords: Akt; Apoptosis; Bad; Mcl-1; Nasopharyngeal carcinoma; Trans-vaccenic acid.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Nasopharyngeal Neoplasms / drug therapy*
  • Oleic Acids / pharmacology
  • Oleic Acids / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • bcl-Associated Death Protein / antagonists & inhibitors
  • bcl-Associated Death Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAD protein, human
  • Oleic Acids
  • bcl-Associated Death Protein
  • Proto-Oncogene Proteins c-akt
  • 11-octadecenoic acid