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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 18

PMID 23593287

Citations 10

Authors

Wei Wang

Fang Gu

Cai Wei

Yigui Tang

Xin Zheng

Mingqiang Ren

Yide Qin

Affiliations

Soon will be listed here.

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 SKOV(3) 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.

Citing Articles

Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment.

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Bioactive milk peptides: an updated comprehensive overview and database.

Nielsen S, Liang N, Rathish H, Kim B, Lueangsakulthai J, Koh J Crit Rev Food Sci Nutr. 2023; 64(31):11510-11529.

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Peptidomic changes in human serous colorectal cancer patients.

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Preparation and identification of anti-breast cancer cells peptides released from yak milk casein.

Gu H, Liang L, Zhu Z, Mao X Front Nutr. 2022; 9:997514.

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

Guo R, Xu Q, Liu L, Liu H, Liu Y, Wei W J Cancer. 2021; 12(20):6081-6093.

PMID: 34539881 PMC: 8425193. DOI: 10.7150/jca.62285.

References

Gill H, Doull F, Rutherfurd K, Cross M . Immunoregulatory peptides in bovine milk. Br J Nutr. 2001; 84 Suppl 1:S111-7. DOI: 10.1017/s0007114500002336. View

Almansour N, Pirogova E, Coloe P, Cosic I, Istivan T . A bioactive peptide analogue for myxoma virus protein with a targeted cytotoxicity for human skin cancer in vitro. J Biomed Sci. 2012; 19:65. PMC: 3407504. DOI: 10.1186/1423-0127-19-65. View

Takada K, Zhu D, Bird G, Sukhdeo K, Zhao J, Mani M . Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012; 4(148):148ra117. PMC: 3631420. DOI: 10.1126/scitranslmed.3003808. View

Raucher D, Moktan S, Massodi I, Bidwell 3rd G . Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides. Expert Opin Drug Deliv. 2009; 6(10):1049-64. DOI: 10.1517/17425240903158909. View

Istivan T, Pirogova E, Gan E, Almansour N, Coloe P, Cosic I . Biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells. PLoS One. 2011; 6(9):e24809. PMC: 3176275. DOI: 10.1371/journal.pone.0024809. View

Li J, Zhang J, He H, Ma Z, Nie Z, Wang Z . Apoptosis in human hepatoma HepG2 cells induced by corn peptides and its anti-tumor efficacy in H22 tumor bearing mice. Food Chem Toxicol. 2012; 51:297-305. DOI: 10.1016/j.fct.2012.09.038. View

Kreider R, Iosia M, Cooke M, Hudson G, Rasmussen C, Chen H . Bioactive properties and clinical safety of a novel milk protein peptide. Nutr J. 2011; 10:99. PMC: 3196694. DOI: 10.1186/1475-2891-10-99. View

Li D, Sakashita S, Morishita Y, Kano J, Shiba A, Sato T . Binding of lactoferrin to IGBP1 triggers apoptosis in a lung adenocarcinoma cell line. Anticancer Res. 2011; 31(2):529-34. View

Muro Urista C, Alvarez Fernandez R, Riera Rodriguez F, Arana Cuenca A, Tellez Jurado A . Review: Production and functionality of active peptides from milk. Food Sci Technol Int. 2011; 17(4):293-317. DOI: 10.1177/1082013211398801. View

10.

Meisel H, FitzGerald R . Biofunctional peptides from milk proteins: mineral binding and cytomodulatory effects. Curr Pharm Des. 2003; 9(16):1289-95. DOI: 10.2174/1381612033454847. View

11.

Spadaro M, Curcio C, Varadhachary A, Cavallo F, Engelmayer J, Blezinger P . Requirement for IFN-gamma, CD8+ T lymphocytes, and NKT cells in talactoferrin-induced inhibition of neu+ tumors. Cancer Res. 2007; 67(13):6425-32. DOI: 10.1158/0008-5472.CAN-06-4080. View

12.

Bishop E, Badve S, Morimiya A, Saxena R, Ulbright T . Apoptosis in spermatocytic and usual seminomas: a light microscopic and immunohistochemical study. Mod Pathol. 2007; 20(10):1036-44. DOI: 10.1038/modpathol.3800933. View

13.

Riedl S, Zweytick D, Lohner K . Membrane-active host defense peptides--challenges and perspectives for the development of novel anticancer drugs. Chem Phys Lipids. 2011; 164(8):766-81. PMC: 3220766. DOI: 10.1016/j.chemphyslip.2011.09.004. View

14.

Jaziri M, Keddad K, Morgat J, Jolles P . Specific binding sites on human phagocytic blood cells for Gly-Leu-Phe and Val-Glu-Pro-Ile-Pro-Tyr, immunostimulating peptides from human milk proteins. Biochim Biophys Acta. 1992; 1160(3):251-61. DOI: 10.1016/0167-4838(92)90085-r. View

15.

Floch F, Jolles P . Biologically active casein peptides implicated in immunomodulation. J Dairy Res. 1989; 56(3):357-62. DOI: 10.1017/s0022029900028806. View

16.

Kitazawa H, Yonezawa K, Tohno M, Shimosato T, Kawai Y, Saito T . Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s) for monocytes and macrophages. Int Immunopharmacol. 2007; 7(9):1150-9. PMC: 3205927. DOI: 10.1016/j.intimp.2007.04.008. View

17.

Xiao Y, Li J, Shi H, Liu J, Feng Y, Li M . [Predictive value of in vitro MTT assay chemosensitivity test of cytotoxic drug activity in cervical cancer]. Ai Zheng. 2007; 26(4):386-9. View

18.

Nagpal R, Behare P, Rana R, Kumar A, Kumar M, Arora S . Bioactive peptides derived from milk proteins and their health beneficial potentials: an update. Food Funct. 2011; 2(1):18-27. DOI: 10.1039/c0fo00016g. View

19.

Fiedorowicz E, Jarmolowska B, Iwan M, Kostyra E, Obuchowicz R, Obuchowicz M . The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs). Peptides. 2010; 32(4):707-12. DOI: 10.1016/j.peptides.2010.12.003. View

20.

Yan J, Wang Z, Yang H, Liu H, Mi S, Lv X . Timing is critical for an effective anti-metastatic immunotherapy: the decisive role of IFNγ/STAT1-mediated activation of autophagy. PLoS One. 2011; 6(9):e24705. PMC: 3172290. DOI: 10.1371/journal.pone.0024705. View