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

Zhou, Juan; Zhao, Min; Tang, Yigui; Wang, Jing; Cai, Wei; Gu, Fei; Lei, Ting; Chen, Zhiwu; Qin, Yide

doi:10.1186/s12885-016-2281-6

Cited by 15 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteins of human milk, in addition to their nutritional role, have a wide variety of physiological functions, for example, intracellular calcium transport, modulation of the immune system, regulation of cell proliferation, and protection from pathogens [1,2,3]. The milk-derived fusion peptide, ACFP, suppresses the growth of primary human ovarian cancer cells by regulating apoptotic gene expression and signaling pathways [4,5]. Furthermore, it is known that human milk contains proteins and peptides capable of killing cancer cells [6,7,8,9].…”

Section: Introductionmentioning

confidence: 99%

Structural and Aggregation Features of a Human κ-Casein Fragment with Antitumor and Cell-Penetrating Properties

et al. 2019

View full text Add to dashboard Cite

Intrinsically disordered proteins play a central role in dynamic regulatory and assembly processes in the cell. Recently, a human κ-casein proteolytic fragment called lactaptin (8.6 kDa) was found to induce apoptosis of human breast adenocarcinoma MCF-7 and MDA-MB-231 cells with no cytotoxic activity toward normal cells. Earlier, we had designed some recombinant analogs of lactaptin and compared their biological activity. Among these analogs, RL2 has the highest antitumor activity, but the amino acid residues and secondary structures that are responsible for RL2′s activity remain unclear. To elucidate the structure–activity relations of RL2, we studied the structural and aggregation features of this fairly large intrinsically disordered fragment of human milk κ-casein by a combination of physicochemical methods: NMR, paramagnetic relaxation enhancement (PRE), Electron Paramagnetic Resonance (EPR), circular dichroism, dynamic light scattering, atomic force microscopy, and a cytotoxic activity assay. It was found that in solution, RL2 exists as stand-alone monomeric particles and large aggregates. Whereas the disulfide-bonded homodimer turned out to be more prone to assembly into large aggregates, the monomer predominantly forms single particles. NMR relaxation analysis of spin-labeled RL2 showed that the RL2 N-terminal region, which is essential not only for multimerization of the peptide but also for its proapoptotic action on cancer cells, is more ordered than its C-terminal counterpart and contains a site with a propensity for α-helical secondary structure.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural and Aggregation Features of a Human κ-Casein Fragment with Antitumor and Cell-Penetrating Properties

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This study also reported that CPE can be used as an antioxidant and bacteriostatic agent. Zhou et al (2016) checked the destructive functionality of the bovine milk peptide-ACFP against ovarian cancer cells and found it to be effective in apoptosis promotion and for viability inhibition of the cells. Sah et al (2014) conducted an investigation focused on evaluating the effect of probiotic strains on anticancer activity.…”

Section: Dairy Sourcesmentioning

confidence: 99%

Food-Derived Anticancer Peptides: A Review

Sharma

Kaur

Kehinde

et al. 2020

Int J Pept Res Ther

View full text Add to dashboard Cite

Cancer has gained appreciable attention in the category of noncommunicable health disorders as the group of proliferative diseases and metabolic syndromes of fatal consequence, globally. The conventional chemotherapeutic, radiological and associated pharmacotherapeutic advances for its cure have timelessly displayed severe aftereffects in patients. Furthermore, the underlying costs and technical requirements of these have added to their limitation recitals. Food-derived bioactive peptides have been scientifically proven as suitable alternatives for cancer management. Studies have shown that some attributes they possess such as specificity, smaller sizes, better ease of syntheses and modification, and improved penetration into cell membranes make them better alternatives to some protein isolates. Their comparative precedencies with regards to natural and efficacy with minimal side effects have offered them the recognition as proficient options in cancer therapy. This review integrates contemporary technical information about bioactive peptides from plants and animal foods and food by-products and their experimentally determined potentials as remedies for cancer. Furthermore, technical details about their isolation methodologies are offered. This article is an augmentation to technical literatures on the cancer subject and an academic exposure of the food-originated approach for its management.

show abstract

“…In recent years, milk-derived bioactive peptides have become a focus of anti-cancer medical research. Some studies have found that milk-derived bioactive peptides have an important role in immune regulation and anti-tumor 17 , 18 . Studies have also found that some bioactive peptides also play a role in enhancing the sensitivity of cancer cells to chemotherapeutic drugs and reversing the resistance of cancer cells 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

“…We found in previous experiments that PGPIPN could effectively reduce inflammation and promote the immune of body, thereby reducing alcoholic liver injury 22 , 23 . It also can inhibit the proliferation, invasion and metastasis of ovarian cancer cells and induce the cells apoptosis 18 , 24 , 25 . At the same time, our research indicated that PGPIPN had no toxic side effects on normal cells (non-transformed cells), but its anticancer efficiency was inferior to traditional chemotherapy drugs, such as DDP.…”

Section: Introductionmentioning

confidence: 99%

Bioactive Hexapeptide Reduced the Resistance of Ovarian Cancer Cells to DDP by Affecting HSF1/HSP70 Signaling Pathway

Guo

Liu

et al. 2021

J. Cancer

Self Cite

View full text Add to dashboard Cite

Ovarian cancer is the leading cause of death in gynecologic malignancies. Ovarian cancer as a metastatic malignant tumor is highly recurrent and prone to drug resistance. Bioactive peptides are an emerging area of biomedical research in reducing resistance of tumor cell to drugs. In this paper, we investigated the effects and mechanisms of bioactive hexapeptide (PGPIPN) derived in milk protein on the sensitivity of ovarian cancer cells to cis-dichlorodiammine platinum (DDP). Human ovarian cancer cell lines (SKOV3 and COC1), their DDP-resistant sublines (SKOV3/DDP and COC1/DDP) and human primary ovarian cancer cells were cultured in vitro under the combined treatment of DDP (close to IC50) and different concentrations of PGPIPN. The viabilities, apoptosis and cell cycle changes were respectively measured by WST-8 and flow cytometry. The mRNA and protein expression levels of HSF1, HSP70, MDR1, ERCC1 and β-actin gene were respectively assayed by RT-qPCR and western blotting. The results showed that PGPIPN significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro. But the effects in sensitive cells were lower than DDP-resistant cells. PGPIPN significantly changed the cell cycles in all human ovarian cancer cells, which leaded to a significant increase in the percentage of cells blocked at G2/M phase and decrease the percentage of cells at G1 phases in a dose-dependent manner. PGPIPN affected the expression levels of HSF1, HSP70, MDR1 and ERCC1 genes. Compared with cells in DDP treatment alone, the expression levels of HSF1 and HSP70 in human ovarian cancer cells treated with DDP and PGPIPN together significantly decreased in dose-dependent manner. PGPIPN significantly decreased MDR1 and ERCC1 of drug-resistant ovarian cancer cell lines and human primary ovarian cancer cell in a dose-dependent manner. Pifithrin-μ (PFTμ, HSP70 inhibitor) decreased or removed the effects of peptide in increasing the sensitivity of ovarian cancer cells to DDP. This suggests that PGPIPN enhanced the sensitivity of ovarian cancer cells to DDP partially via reducing the activity of HSF1/HSP70 signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage.

show abstract

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

Cited by 15 publications

References 31 publications

Structural and Aggregation Features of a Human κ-Casein Fragment with Antitumor and Cell-Penetrating Properties

Structural and Aggregation Features of a Human κ-Casein Fragment with Antitumor and Cell-Penetrating Properties

Food-Derived Anticancer Peptides: A Review

Bioactive Hexapeptide Reduced the Resistance of Ovarian Cancer Cells to DDP by Affecting HSF1/HSP70 Signaling Pathway

Contact Info

Product

Resources

About