PGPIPN, a Therapeutic Hexapeptide, Suppressed Human Ovarian Cancer Growth by Targeting BCL2

Abstract

Bioactive peptides, either derived from nature resources or synthesized by rational design, have been demonstrated potential for therapeutic agents against numerous human diseases, including cancer. However, the mechanism of therapeutic peptides against cancer has not been well elucidated. Here we show that PGPIPN, a hexapeptide derived from bovine β-casein, inhibited the proliferation of human ovarian cancer cells line SKOV3 as well as the primary ovarian cancer cells in vitro. Consistently, PGPIPIN also decreased tumor growth rate in xenograft ovarian cancer model mice in a dose-dependent manner. Further study demonstrated that the anti-tumor effect of PGPIPN is partially through promoting cell apoptosis by inhibiting BCL2 pathway. Thus, our study suggests that PGPIPN is a potential therapeutic agent for the treatment of ovarian cancer or other types of cancer.

The milk-derived fusion peptide, ACFP, suppresses the growth of primary human ovarian cancer cells by regulating apoptotic gene expression and signaling pathways

“…The hexapeptide (Pro-Gly-Pro-Ile-Pro-Asn, PGPIPN, 63–68 residues of bovine ß-casein), also known as immune hexapeptide or immunomodulating peptide, was isolated from hydrolysate of bovine β casein and has been shown to elicit an immune response in cancer cells [ 7 – 10 ]. In line with this finding, our research group recently showed that PGPIPN inhibited the growth of SKOV3 cells in vitro and promoted apoptosis and decreased tumor growth in a xenograft ovarian cancer model [ 11 ]. However, the anti-cancer effects of PGPIPN are significantly lower than those of classical anti-cancer drugs, such as paclitaxel or 5-fluorouracil (5-FU) [ 11 ].…”

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

“…However, the inhibition effects of PGPIPN were less than that of DDP (a conventional anticancer drug) as the positive control. However, our early studies (9) showed that DDP not only significantly inhibited ovarian cancer cell proliferation, but also had a strong side effect on untransformed normal cells. We showed that PGPIPN had no, or slight side effects on untransformed normal cells by MTT assay of human normal hepatic cell line LO2, murine embryo fibroblast cells (MEFs) and para-carcinoma tissues of human ovarian cancer.…”

“…Our previous studies showed that PGPIPN significantly decreased the growth of xenografted human ovarian tumor in vivo, and induced human ovarian cancer cell apoptosis (9). However, there is no report on whether this peptide could resist the invasion and migration of human ovarian cancer cells or not.…”

“…Although these bioactive peptides were not as effective as chemotherapy drugs such as DDP in the treatment of cancer, they have no toxicity, or low toxicity to normal cells (untransformed cells). Thus they have a broad prospect and potential for the development as anticancer drugs (8,9).…”

Anticancer and antiproliferative properties of food-derived protein hydrolysates and peptides

“…The hydrolysates are usually composed of active and non-active peptides; therefore, further processing to obtain fractions that are enriched with active fractions may be carried out (Doyen et al, 2011;Perego et al, 2011). In some cases, the active peptide fractions are subjected to additional separation and purification protocols that yield homogenous peptides suitable for amino acid sequence analysis (Hung et al 2014;Ma et al 2015;Pan et al, 2016;Wang and Zhang, 2017;Wang et al, 2013;You et al, 2011).…”