A REVIEW OF POTENTIAL ANTICANCERS FROM ANTIMICROBIAL PEPTIDES


Khamsah Suryati Mohd, Mohammed Al-kassim Hassan, Wan-atirah Azemin, Saravanan Dharmaraj

Abstract


Cancer is one of the leading causes of morbidity and mortality globally. The drawbacks of conventional chemotherapy such as resistance, lack of specificity, severe toxicity warrant the need to explore alternative approach for the treatment of cancer. Antimicrobial peptides are part of the innate defense mechanism of all organisms and have been developed as potential alternatives in combatting infectious diseases. In addition, anticancer effects of many peptides have been reported with remarkable prospects in some in vitro studies especially on breast, cervical and lung cancer cell lines, and in vivo murine tumour xenografts. This review summarizes the reports on the activities of some selected anticancer peptides on various cancer cell lines.


Keywords


Antimicrobial peptides, Anticancer/antitumour peptides, Host defense peptides

| PDF | HTML |

References


Xiao X, Wang P, Lin W, Jia J, Chou K. iAMP-2L: A two-level multi-label classifier for identifying antimicrobial peptides and their functional types. Anal Biochem 2013;436:168–77.

Seo M, Won H, Kim J, Mishig-ochir T, Lee B. Antimicrobial peptides for therapeutic applications: a review. Mol 2012;17:12276–86.

Zasloff M. Antimicrobial peptides of multicellular organisms. Nat 2002;415:389–95.

Pushpanathan M, Gunasekaran P, Rajendhran J. Antimicrobial Peptides: versatile biological properties. Int J Pept 2013;2013:1–15.

Kamysz W, Okrój M, Łukasiak J. Novel properties of antimicrobial peptides. Acta Biochim Pol 2003;50:461–9.

Pasupuleti M, Schmidtchen A, Malmsten M. Antimicrobial peptides: key components of the innate immune system. Crit Rev Biotechnol 2012;32:143–71.

Wang G. Human antimicrobial peptides and proteins. Pharm 2014;7:545–94.

Li Y, Xiang Q, Zhang Q, Huang Y, Su Z. Overview on the recent study of antimicrobial peptides: origins, functions, relative mechanisms and application. Pept 2012;37:207–15.

Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol 2013;36:697–705.

Aerts AM, Franåois IEJA, Cammue BPA, Thevissen K. Review The mode of antifungal action of plant, insect and human defensins. Cell Mol Life Sci 2008;65:2069–79.

Václav Č, Bém R. Lucifensins, the insect defensins of biomedical importance: the story behind the maggot therapy. Pharm 2014;7:251–64.

Koo JC, Lee SY, Chun HJ, Cheong YH, Choi JS, Kawabata SI, et al. Two hevein homologs isolated from the seed of Pharbitis nil L. exhibit potent antifungal activity. Biochim Biophys Acta-Protein Struct Mol Enzymol 1998;1382:80–90.

Orrù S, Scaloni A, Giannattasio M, Urech K, Pucci P, Schaller G. Amino acid sequence, S-S bridge arrangement and distribution in plant tissues of thionins from Viscum album. Biol Chem 1997;378:989–96.

Sharma S, Verma HN, Sharma NK. Cationic bioactive peptide from the seeds of Benincasa hispida. Int J Pept 2014;2014:1–12.

Huang PH, Chen JY, Kuo CM. Three different hepcidins from tilapia, Oreochromis mossambicus: analysis of their expressions and biological functions. Mol Immunol 2007;44:1922–34.

Buonocore F, Randelli E, Casani D, Picchietti S, Belardinelli MC, de Pascale D, et al. A piscidin-like antimicrobial peptide from the icefish Chionodraco hamatus (Perciformes: Channichthyidae): molecular characterization, localization and bactericidal activity. Fish Shellfish Immunol 2012;33:1183–91.

Cho JH, Sung BH, Kim SC. Buforins: histone H2A-derived antimicrobial peptides from toad stomach. Biochim Biophys Acta 2009;1788:1564–9.

Conlon JM, Mechkarska M, Lukic ML, Flatt PR. Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents. Pept 2014;57:67–77.

Coronado MA, Georgieva D, Buck F, Gabdoulkhakov AH, Ullah A, Spencer PJ, et al. Purification, crystallization and preliminary X-ray diffraction analysis of crotamine, a myotoxic polypeptide from the Brazilian snake Crotalus durissus terrificus. Acta Crystallogr Sect F Struct Biol Cryst Commun 2012;68:1052–4.

Wang Y, Hong J, Liu X, Yang H, Liu R, Wu J, et al. Snake cathelicidin from Bungarus fasciatus is a potent peptide antibiotics. PLoS One 2008;3:e3217.

Stegemann C, Kolobov A, Leonova YF, Knappe D, Shamova O, Ovchinnikova TV, et al. Isolation, purification and de novo sequencing of TBD-1, the first beta-defensin from leukocytes of reptiles. Proteomics 2009;9:1364–73.

Zhang G, Sunkara LT. Avian antimicrobial host defense peptides: from biology to therapeutic applications. Pharm 2014;7:220–47.

Wu J, Gao B, Zhu S. The fungal defensin family enlarged. Pharm 2014;7:866–80.

Xiong YQ, Hady WA, Deslandes A, Rey A, Fraisse L, Kristensen HH, et al. Efficacy of NZ2114, a novel plectasin-derived cationic antimicrobial peptide antibiotic, in experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2011;55:5325–30.

Gyawali R, Ibrahim SA. Natural products as antimicrobial agents. Food Control 2014;46:412–29.

Lee DG, Hahm K-S, Park Y, Kim H-Y, Lee W, Lim S-C, et al. Functional and structural characteristics of anticancer peptide Pep27 analogues. Cancer Cell Int 2005;5:21.

McManus AM, Dawson NF, Wade JD, Carrington LE, Winzor DJ, Craik DJ. Three-dimensional structure of RK-1:a novel alpha-defensin peptide. Biochem 2000;39:15757–64.

Jenssen H, Hamill P, Hancock REW. Peptide antimicrobial agents. Clin Microbiol Rev 2006;19:491–511.

Hancock REW, Sahl H-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 2006;24:1551–7.

Yang P, Ramamoorthy A, Chen Z. Membrane orientation of MSI-78 measured by sum frequency generation vibrational spectroscopy. Langmuir 2011;27:7760–7.

Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 2005;3:238–50.

Pouny Y, Rapaport D, Mor A, Nicolas P, Shai Y. Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes. Biochem 1992;31:12416–23.

Zhang L, Rozek A, Hancock RE. Interaction of cationic antimicrobial peptides with model membranes. J Biol Chem 2001;276:35714–22.

Silva PM, Gonçalves S, Santos NC. Defensins: antifungal lessons from eukaryotes. Front Microbiol 2014;5:1–17.

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:2011–30.

Papo N, Shai Y. Host defense peptides as new weapons in cancer treatment. Cell Mol Life Sci 2005;62:784–90.

Gaspar D, Veiga AS, Castanho MARB. From antimicrobial to anticancer peptides. A review. Front Microbiol 2013;4:294.

Oren Z, Shai Y. Mode of action of linear amphipathic alpha-helical antimicrobial peptides. Biopolymers 1998;47:451–63.

Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta-Biomembr 1999;1462:55–70.

Mai JC, Mi Z, Kim SH, Ng B, Robbins PD. A proapoptotic peptide for the treatment of solid tumors. Cancer Res 2001;61:7709–12.

Hwang C, Heath EI. Angiogenesis inhibitors in the treatment of prostate cancer. J Hematol Oncol 2010;3:1–12.

Starzec A, Vassy R, Martin A, Lecouvey M, Di Benedetto M, Crépin M, et al. Antiangiogenic and antitumor activities of peptide inhibiting the vascular endothelial growth factor binding to neuropilin-1. Life Sci 2006;79:2370–81.

Wu D, Gao Y, Chen L, Qi Y, Kang Q, Wang H, et al. Anti-tumor effects of a novel chimeric peptide on S180 and H22 xenografts bearing nude mice. Pept 2010;31:850–64.

Wu D, Gao Y, Qi Y, Chen L, Ma Y, Li Y. Peptide-based cancer therapy: opportunity and challenge. Cancer Lett 2014;351:13–22.

Schweizer F. Cationic amphiphilic peptides with cancer-selective toxicity. Eur J Pharmacol 2009;625:190–4.

Li J-T, Zhang J-L, He H, Ma Z-L, Nie Z-K, Wang Z-Z, et al. Apoptosis in human hepatoma HepG2 cells induced by corn peptides and its anti-tumor efficacy in H22 tumor bearing mice. Food Chem Toxicol 2013;51:297–305.

Xue Z, Liu Z, Wu M, Zhuang S, Yu W. Effect of rapeseed peptide on DNA damage and apoptosis in Hela cells. Exp Toxicol Pathol 2010;62:519–23.

Prasanthi K, Lily Y. Apoptosis signaling pathway and resistance to apoptosis in breast cancer stem cells. In: George GC, Lai PBS(eds) Apoptosis in carcinogenesis and Chemotherapy. Springer Science & Business Media; 2009.

Fang XY, Chen W, Fan JT, Song R, Wang L, Gu YH, et al. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction. Toxicol Appl Pharmacol 2013;267:95–103.

Liu J-J, Lin M, Yu J-Y, Liu B, Bao J-K. Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett 2011;300:105–14.

Fernandez DI, Sani M, Miles AJ, Wallace BA, Separovic F. Membrane defects enhance the interaction of antimicrobial peptides, aurein 1.2 versus caerin 1.1. BBA-Biomembr 2013;1828:1863–72.

Chang W-T, Pan C-Y, Rajanbabu V, Cheng C-W, Chen J-Y. Tilapia (Oreochromis mossambicus) antimicrobial peptide, hepcidin 1-5, shows antitumor activity in cancer cells. Pept 2011;32:342–52.

Aoki W, Ueda M. Characterization of antimicrobial peptides toward the development of novel antibiotics. Pharm 2013;6:1055–81.

Lin W-J, Chien Y-L, Pan C-Y, Lin T-L, Chen J-Y, Chiu S-J, et al. Epinecidin-1, an antimicrobial peptide from fish (Epinephelus coioides) which has an antitumor effect like lytic peptides in human fibrosarcoma cells. Pept 2009;30:283–90.

Chen J, Xu X, Underhill CB, Yang S, Wang L. Tachyplesin activates the classic complement pathway to kill tumor cells. Cancer Res 2005;65:4614–22.

Huang C-Y, Huang H-Y, Forrest MD, Pan Y-R, Wu W-J, Chen H-M. Inhibition effect of a custom peptide on lung tumors. PLoS One 2014;9:e109174.

Pepe G, Tenore GC, Mastrocinque R, Stusio P, Campiglia P. Potential anticarcinogenic peptides from bovine milk. J Amino Acids 2013;2013:939804.

Guo X, Ma C, Du Q, Wei R, Wang L, Zhou M, et al. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities. Biochim 2013;95:1784–94.

Conlon JM, Mechkarska M. Host-defense peptides with therapeutic potential from skin secretions of frogs from the family pipidae. Pharm 2014;7:58–77.

Rodrigues EG, Dobroff ASS, Cavarsan CF, Paschoalin T, Nimrichter L, Mortara RA, et al. Effective topical treatment of subcutaneous murine B16F10-NEX2 melanoma by the antimicrobial peptide gomesin. Neoplasia 2008;10:61–8.

Wang C, Zhou Y, Li S, Li H, Tian L, Wang H, et al. Anticancer mechanisms of temporin-1CEa, an amphipathic α-helical antimicrobial peptide, in Bcap-37 human breast cancer cells. Life Sci 2013;92:1004–14.

Vad BS, Bertelsen K, Johansen CH, Pedersen JM, Skrydstrup T, Nielsen NC, et al. Pardaxin permeabilizes vesicles more efficiently by pore formation than by disruption. Biophys J 2010;98:576–85.

Kim J-K, Lee S-A, Shin S, Lee J-Y, Jeong K-W, Nan YH, et al. Structural flexibility and the positive charges are the key factors in bacterial cell selectivity and membrane penetration of peptoid-substituted analog of Piscidin1. Biochim Biophys Acta 2010;1798:1913–25.

Chen Y-LS, Li J-H, Yu C-Y, Lin C-J, Chiu P-H, Chen P-W, et al. Novel cationic antimicrobial peptide GW-H1 induced caspase-dependent apoptosis of hepatocellular carcinoma cell lines. Pept 2012;36:257–65.

Bechinger B. Structure and functions of channel-forming peptides: Magainins, cecropins, melittin and alamethicin. J Membr Biol 1997;156:197–211.

Huang Y-B, He L-Y, Jiang H-Y, Chen Y-X. Role of helicity on the anticancer mechanism of action of cationic-helical peptides. Int J Mol Sci 2012;13:6849–62.

Huang Y-B, Wang X-F, Wang H-Y, Liu Y, Chen Y. Studies on mechanism of action of anticancer peptides by modulation of hydrophobicity within a defined structural framework. Mol Cancer Ther 2011;10:416–26.

Suttmann H, Retz M, Paulsen F, Harder J, Zwergel U, Kamradt J, et al. Antimicrobial peptides of the cecropin-family show potent antitumor activity against bladder cancer cells. BMC Urol 2008;8:5.

Wu J-M, Jan P-S, Yu H-C, Haung H-Y, Fang H-J, Chang Y-I, et al. Structure and function of a custom anticancer peptide, CB1a. Pept 2009;30:839–48.

Lehmann J, Retz M, Sidhu SS, Suttmann H, Sell M, Paulsen F, et al. Antitumor activity of the antimicrobial peptide magainin II against bladder cancer cell lines. Eur Urol 2006;50:141–7.

Miyazaki Y, Aoki M, Yano Y, Matsuzaki K. Interaction of antimicrobial peptide magainin 2 with gangliosides as a target for human cell binding. Biochem 2012;51:10229–35.

Soballe PW, Maloy WL, Myrga ML, Jacob LS, Herlyn M. Experimental local therapy of human melanoma with lytic magainin peptides. Int J Cancer 1995;60:280–4.

Ohsaki Y, Gazdar AF, Chen H, Johnson BE. Antitumor activity of magainin analogues against human lung cancer cell lines. Cancer Res 1992;52:3534–8.

Baker MA, Maloy WL, Zasloff M, Jacob LS. Anticancer efficacy of magainin2 and analogue peptides. Cancer Res 1993;53:3052–7.

Bessalle R, Kapitkovsky A, Gorea A, Shalit I, Fridkin M. All-D-magainin: Chirality, antimicrobial activity and proteolytic resistance. FEBS Lett 1990;274:151–5.

Moon D-O, Park S-Y, Heo M-S, Kim K-C, Park C, Ko WS, et al. Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. Int Immunopharmacol 2006;6:1796–807.

Slaninová J, Mlsová V, Kroupová H, Alán L, Tůmová T, Monincová L, et al. Toxicity study of antimicrobial peptides from wild bee venom and their analogs toward mammalian normal and cancer cells. Pept 2012;33:18–26.

Sørensen OE, Follin P, Johnsen AH, Calafat J, Sandra Tjabringa G, Hiemstra PS, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 2001;97:3951–9.

Okumura K, Itoh A, Isogai E, Hirose K, Hosokawa Y, Abiko Y, et al. C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells. Cancer Lett 2004;212:185–94.

Li X, Li Y, Han H, Miller DW, Wang G. Solution structures of human ll-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region. J Am Chem Soc 2006;128:5776–85.

Johansson J, Gudmundsson GH, Rottenberg ME, Berndt KD, Agerberth B. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem 1998;273:3718–24.

Wu S-P, Huang T-C, Lin C-C, Hui C-F, Lin C-H, Chen J-Y. Pardaxin, a fish antimicrobial peptide, exhibits antitumor activity toward murine fibrosarcoma in vitro and in vivo. Mar Drugs 2012;10:1852–72.

Huang T-C, Lee J-F, Chen J-Y. Pardaxin, an antimicrobial peptide, triggers caspase-dependent and ROS-mediated apoptosis in HT-1080 cells. Mar Drugs 2011;9:1995–2009.

Hsu JC, Lin LC, Tzen JTC, Chen JY. Pardaxin-induced apoptosis enhances antitumor activity in HeLa cells. Pept 2011;32:1110–6.

Al-Benna S, Shai Y, Jacobsen F, Steinstraesser L. Oncolytic activities of host defense peptides. Int J Mol Sci 2011;12:8027–51.

Lee HS, Park CB, Kim JM, Jang SA, Park IY, Kim MS, et al. Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Lett 2008;271:47–55.

Rozek T, Wegener KL, Bowie JH, Olver IN, Carver JA, Wallace JC, et al. The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis: The solution structure of aurein 1.2. Eur J Biochem 2000;267:5330–41.

Hilchie AL, Doucette CD, Pinto DM, Patrzykat A, Douglas S, Hoskin DW. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts. Breast Cancer Res 2011;13:R102.

Hou L, Zhao X, Wang P, Ning Q, Meng M, Liu C. Antitumor activity of antimicrobial peptides containing CisoDGRC in CD13 negative breast cancer cells. PLoS One 2013;8:e53491.

Wang C, Tian LL, Li S, Li HB, Zhou Y, Wang H, et al. Rapid cytotoxicity of antimicrobial peptide tempoprin-1cea in breast cancer cells through membrane destruction and intracellular calcium mechanism. PLoS One 2013;8:e60462.

Masso-Silva JA, Diamond G. Antimicrobial peptides from fish. Pharm 2014;7:265–310.

Chen J-Y, Lin W-J, Lin T-L. A fish antimicrobial peptide, tilapia hepcidin TH2-3, shows potent antitumor activity against human fibrosarcoma cells. Pept 2009;30:1636–42.

Chen J-Y, Lin W-J, Wu J-L, Her GM, Hui C-F. Epinecidin-1 peptide induces apoptosis which enhances antitumor effects in human leukemia U937 cells. Pept 2009;30:2365–73.

Lin H-J, Huang T-C, Muthusamy S, Lee J-F, Duann Y-F, Lin C-H. Piscidin-1, an antimicrobial peptide from fish (hybrid striped bass Morone saxatilis x M. chrysops), induces apoptotic and necrotic activity in HT1080 cells. Zoolog Sci 2012;29:327–32.

Xu H, Chen CX, Hu J, Zhou P, Zeng P, Cao CH, et al. Dual modes of antitumor action of an amphiphilic peptide A(9)K. Biomaterials 2013;34:2731–7.

Yoo Y-C, Watanabe R, Koike Y, Mitobe M, Shimazaki K, Watanabe S, et al. Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived Peptide: involvement of reactive oxygen species. Biochem Biophys Res Commun 1997;237:624–8.

Tone Eliassen L, Berge G, Sveinbjørnsson B, Svendsen JS, Vorland LH, Rekdal Ø. Evidence for a direct antitumor mechanism of action of bovine lactoferricin. Anticancer Res 2002;22:2703–10.

Mader JS, Salsman J, Conrad DM, Hoskin DW. Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Mol Cancer Ther 2005, 4:612–24.

Eliassen LT, Berge G, Leknessund A, Wikman M, Lindin I, Løkke C, et al. The antimicrobial peptide, Lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo. Int J Cancer 2006;119:493–500.

Furlong SJ, Mader JS, Hoskin DW. Lactoferricin-induced apoptosis in estrogen-nonresponsive MDA-MB-435 breast cancer cells is enhanced by C6 ceramide or tamoxifen. Oncol Rep 2006;15:1385–90.

Risso A, Zanetti M, Gennaro R. Cytotoxicity and apoptosis mediated by two peptides of innate immunity. Cell Immunol 1998;189:107–15.

Risso A, Braidot E, Sordano MC, Vianello A, Macrı F, Skerlavaj B, et al. BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore. Mol Cell Biol 2002;22:1926–35.

Skerlavaj B, Gennaro R, Bagella L, Merluzzi L, Risso A, Zanetti M. Biological characterization of two novel cathelicidin-derived peptides and identification of structural requirements for their antimicrobial and cell lytic activities. J Biol Chem 1996;271:28375–81.

Chen Y, Xu X, Hong S, Chen J, Liu N, Underhill CB, et al. RGD-tachyplesin inhibits tumor growth. Cancer Res 2001;61:2434–8.




About this article

Title

A REVIEW OF POTENTIAL ANTICANCERS FROM ANTIMICROBIAL PEPTIDES

Keywords

Antimicrobial peptides, Anticancer/antitumour peptides, Host defense peptides

Date

13-02-2015

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 7, Issue 4, 2015 Page: 19-26

Online ISSN

0975-1491

Statistics

804 Views | 779 Downloads

Authors & Affiliations

Khamsah Suryati Mohd
Faculty of Bioresources and Food Industry, Universiti Sultan Zainal Abidin, Campus Tembila, 22200 Besut, Terengganu, Malaysia
Malaysia

Mohammed Al-kassim Hassan
Universiti Sultan Zainal Abidin
Malaysia

Wan-atirah Azemin
Universiti Sultan Zainal Abidin
Malaysia

Saravanan Dharmaraj
Universiti Sultan Zainal Abidin
Malaysia


Article Tools



Refbacks

  • There are currently no refbacks.