Gastric cancer is one of the most common malignant
cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is an urgent need. It has been reported that
cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and
cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of
peptide fragments derived from bovine
lactoferrin and evaluated their anticancer potency toward the
gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA
peptide fragment,
lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells.
Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64 μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and
poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and
beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved
beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of
caspases cleaved
beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for
gastric cancer.