7α,15-Dihydroxydehydroabietic acid from Pinus koraiensis inhibits the promotion of angiogenesis through downregulation of VEGF, p-Akt and p-ERK in HUVECs

Bioorg Med Chem Lett. 2018 Apr 1;28(6):1084-1089. doi: 10.1016/j.bmcl.2018.02.014. Epub 2018 Feb 9.

Abstract

Pinus koraiensis pinecones are considered an undesired waste by-product of the processing of seeds. However, recent studies of the potential anti-tumor effects of the pinecones have led to increasing interest in their chemical constituents. The present study examined the potential antiangiogenic effects of the constituents of pinecones and further characterized their underlying mechanisms of action. Chemical investigation of a water extract of P. koraiensis pinecones led to the isolation and identification of the eight main components including five diterpenoids (1-5), two monoterpenes (6,7) and a phenolic acid (8). The structure of the compounds was determined by spectroscopic analysis of NMR spectra and LC/MS analysis. Of the isolated compounds, 7α,15-dihydroxydehydroabietic acid (5) significantly inhibited the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5 inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK signaling pathways. These results provide experimental evidence of a novel biological activity of 7α,15-dihydroxydehydroabietic acid (5) as a potential antiangiogenic substance. This study also suggests that compound 5 could potentially be a useful adjuvant therapeutic substance for cancer prevention and treatment.

Keywords: 7α,15-Dihydroxydehydroabietic acid; Angiogenesis; Pinecones; Pinus koraiensis; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemical synthesis
  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • Molecular Structure
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Pinus / chemistry*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Abietanes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • abietic acid