A team of researchers indicate that the peptide fragment
lactoferricin B25 (LFcinB25)
derived from cow's milk exhibited potent anti-cancer capability against human stomach cancer cell cultures.
They determine that LFcinB25 has potential to be a future therapeutic agent for gastric cancer.
Investigators evaluated the effects of three peptide fragments derived from lactoferricin B, a peptide in milk that has antimicrobial properties. Only one of the fragments, LFcinB25 reduced the survival of human AGS (Gastric Adenocarcinoma) cells in a dose-dependent and time-dependent manner.
Under a microscope the investigators could see that after an hour of exposure to the gastric cancer cells, LFcinB25 migrated to the cell membrane of the AGS cells, and within 24 hours the cancer cells had shrunken in size and lost their ability to adhere to surfaces. In the early stages of exposure, LFcinB25 reduced cell viability through both apoptosis (programmed cell death) and autophagy (degradation and recycling of obsolete or damaged cell parts). At later stages, apoptosis appeared to dominate, possibly through caspase-dependent mechanisms, and autophagy waned.
Western blot analysis for the activation of autophagy-related proteins. The AGS cells were treated with lactoferricin B25 (LFcinB25; 64 μM) for 0 to 48 h, and their cellular extracts were detected by Western blotting for JNK-1, Bcl-2, phosphorylated Bcl-2, Beclin 1, cleaved Beclin 1, LC3 I, and LC3 II to see if LFcinB25 induced autophagy of AGS cells. Lane Con = untreated control. β-Actin was used as internal control.
"Gastric cancer is one of the most common causes of cancer-related mortality worldwide, especially in Asian countries," says Wei-Jung Chen, PhD, of the Department of Biotechnology and Animal Science of National Ilan University, Taiwan Republic of China. "In general, the main curative therapies for gastric cancer are surgery and chemotherapy, which are generally only successful if the cancer is diagnosed at an early stage. Novel treatment strategies to improve prognosis are urgently needed.
"This is the first report describing interplay between apoptosis and autophagy in LFcinB-induced cell death of cancer cells."
The research also suggested a target, Beclin-1, which may enhance LFcinB25's cytotoxic action. Beclin-1 is a protein in humans that plays a central role in autophagy, tumor growth, and degeneration of neurons. In this study, the investigators found that cleaved beclin-1 increased in a time-dependent manner after LFcinB25-exposure, suggesting to the authors a new approach in drug development that may boost the anticancer effects of LFcinB25.
"Optimization of LFcinB using various strategies to enhance further selectivity is expected to yield novel anticancer drugs with chemotherapeutic potential for the treatment of gastric cancer," concludes Chen.
Citation: W.-R. Pan, P.-W. Chen, Y.-L.S. Chen, H.-C. Hsu, C.-C. Lin, W.-J. Chen, 'Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage', Journal of Dairy Science 17 October 2013 DOI: 10.3168/jds.2013-7285