Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells

Cell Biochem Funct. 2017 Jan;35(1):33-41. doi: 10.1002/cbf.3242. Epub 2017 Jan 3.

Abstract

Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD+ . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease.

Keywords: HeLa; ROS; apoptosis; caspase; glutathione; lactoferrin.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspases / metabolism
  • Cattle
  • Cell Proliferation / drug effects
  • Glutathione / metabolism
  • HeLa Cells
  • Humans
  • Lactoferrin / toxicity*
  • Microscopy, Confocal
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • NAD / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • NAD
  • Lactoferrin
  • Caspases
  • Glutathione