Effect of Heat Treatment on the Antitumor Activity of Lactoferrin in Human Colon Tumor (HT29) Model

J Agric Food Chem. 2019 Jan 9;67(1):140-147. doi: 10.1021/acs.jafc.8b05131. Epub 2018 Nov 27.

Abstract

To investigate the effect of heat treatment on the antitumor activity of lactoferrin in colon cancer cells and colon tumors, the HT-29 (human intestinal epithelial tumor cell) cell line was exposed to lactoferrin and various heat treatments. The impacts on cell proliferation, invasion, and migration were observed in vitro, and nude mice bearing HT29 tumors were administered lactoferrin and underwent various heat treatments in vivo. In the HT29 cell proliferation test using transwell and scratch analyses, lactoferrin (20 mg/mL) without or with heat treatment (50 and 70 °C) significantly inhibited cell proliferation, migration, and invasion (compared with the control, p < 0.05), while lactoferrin with heat treatment (100 °C) did not affect these parameters. In vivo, HT29 tumor weight was significantly reduced in the lactoferrin (without heat treatment and with 50 and 70 °C treatment) groups (1.59 ± 0.20, 1.67 ± 0.25, and 2.41 ± 0.42 g, compared with the control, p < 0.05), and there was no significant difference between the control (3.73 ± 0.33 g) and the 100 °C treatment group (3.58 ± 0.29 g). Moreover, 100 °C heat treatment reduced inhibition of the VEGFR2/VEGFA/PI3K/Akt/Erk1/2 angiogenesis pathway by lactoferrin. In summary, HT29 tumors were effectively suppressed by lactoferrin via inhibition of VEGFR2/VEGFA/PI3K/Akt/Erk1/2 pathway, and heat treatment affected the antitumor activity of lactoferrin in a temperature-dependent manner.

Keywords: HT29 cell; antitumor activity; heat treatment; lactoferrin; tumor-bearing model.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / physiopathology
  • HT29 Cells
  • Hot Temperature
  • Humans
  • Lactoferrin / administration & dosage*
  • Lactoferrin / chemistry
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Phosphatidylinositol 3-Kinases
  • Vascular Endothelial Growth Factor Receptor-2
  • Lactoferrin