Inhibitory Effects of Pectinase-Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells

J Food Sci. 2019 Nov;84(11):3284-3295. doi: 10.1111/1750-3841.14824. Epub 2019 Oct 16.

Abstract

Pectinase is a well-known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase-treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S-phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL-1539 colon normal cells. Furthermore, PC-induced caspase-dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase-3, caspase-8, and caspase-9, and downregulation of antiapoptotic Bcl-2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary-like tube formation, and angiogenesis from rat aortic rings. HPLC-PDA analysis showed that there were at least four different phenolics including 5-HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities. PRACTICAL APPLICATION: Pectinases are one of the well-known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase-treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase-treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis.

Keywords: Prunus mume; angiogenesis; colorectal cancer; pectinase; phenolic compound.

MeSH terms

  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / physiopathology*
  • Fruit / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydroxybenzoates / chemistry
  • Hydroxybenzoates / pharmacology
  • Phenols / chemistry
  • Phenols / pharmacology
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Polygalacturonase / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Prunus / chemistry*
  • Rats
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Hydroxybenzoates
  • Phenols
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A
  • protocatechuic acid
  • Polygalacturonase