The milk-derived hexapeptide PGPIPN inhibits the invasion and migration of human ovarian cancer cells by regulating the expression of MTA1 and NM23H1 genes

Abstract

Abstract. Some bioactive peptides derived from natural resources or synthesized by rational design have been proved to have very good anticancer effect. We studied the inhibition of PGPIPN, a hexapeptide derived from bovine β-casein, on the invasion and metastasis of human ovarian cancer cells in vitro and its molecular mechanism. The human ovarian cancer cells studied include the cell line SKOV 3 as well as the primary ovarian cancer cells from ovarian tumor tissues of 37 patients at initial debulking surgery, diagnosed as serous ovarian adenocarcinoma. We showed that PGPIPN inhibited the invasion of ovarian cancer cells with Transwell chamber assay, the migration of ovarian cancer cells with cell scratch assay and colony formation of ovarian cancer cells. The expression (mRNAs and proteins) of genes relevant to invasion and metastasis, MTA1, and NM23H1 were analyzed by real-time PCR and western blotting. PGPIPN repressed the expression of MTA1, and promoted NM23H1. The effects of PGPIPN were dose-dependent. Thus, our study suggests that PGPIPN is a potential therapeutic agent for adjuvant therapy of human malignant ovarian tumors.

Anti‐proliferative activity of bovine blood hydrolysates towards cancer cells in culture

“…Recently, a peptide (PGPIPN), isolated from a bovine b-casein hydrolysate and previously reported to have immunomodulatory activity (Migliore-Samour et al, 1989), was studied for its anti-cancer activity. This study found that the peptide inhibited the invasion and migration of ovarian cancer cells in culture and also inhibited in vitro colony formation in these cells (Zhao et al, 2016). A blood-derived compound, valorphin, released by proteolytic cleavage of haemoglobin, has also been reported to have anti-cancer effects.…”

“…It was reported that several of the collagen hydrolysate fractions showed a significant antiproliferative activity and increased caspase-3 activity in cells (Castro et al, 2009). This study found that the peptide inhibited the invasion and migration of ovarian cancer cells in culture and also inhibited in vitro colony formation in these cells (Zhao et al, 2016). Recently, a peptide (PGPIPN), isolated from a bovine b-casein hydrolysate and previously reported to have immunomodulatory activity (Migliore-Samour et al, 1989), was studied for its anti-cancer activity.…”

“…Castro et al (2009) found that a collagen hydrolysate that was 2.5 kDa in size, along with several of its fractions, had a significant inhibitory effect on cell growth. Zhao et al (2016) also found that a peptide from bovine casein containing mostly hydrophobic peptides (PGPIPN) had significant anti-cancer activity. Small di-and tripeptides from marine sources have also been reported to possess anti-proliferative and apoptotic activity (Chi et al, 2015).…”

Therapeutic hexapeptide (PGPIPN) prevents and cures alcoholic fatty liver disease by affecting the expressions of genes related with lipid metabolism and oxidative stress

“…PGPIPN from bovine milk protein has demonstrated various effects including immunoregulation and anti-cancer [ 15 , 16 ]. The milk peptides are safe to consume orally for healthy volunteers and no clinically significant side effects are reported [ 17 ].…”

“…The cancer and normal cells vary greatly in cell membrane proteins and signaling pathways. Our previous studies indicated that PGPIPN could induce apoptosis of ovarian cancer cells [ 15 , 16 ]. This experiment showed that CHOP and Caspase-3 levels were very low in steatosis hepatocyte model established with hepatocellular carcinoma cell HepG2.…”