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Mauriporin, a Novel Cationic α-Helical Peptide with Selective Cytotoxic Activity Against Prostate Cancer Cell Lines from the Venom of the Scorpion Androctonus mauritanicus

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Abstract

Prostate cancer is the second most common cancer in men and the second leading cause of cancer-related deaths among men in the western world. Finding a cure for prostate cancer is urgently needed. Scorpion venoms are rich sources of biologically active peptides, among which the non-disulfide bridged peptides constitute an important group displaying multifunctional activities. The non-disulfide bridged scorpion venom peptides are rarely identified and poorly characterized so far. In this work, we report the molecular cloning and functional characterization of a novel non-disulfide bridged peptide from the venomous gland cDNA library of the Moroccan scorpion Androctonus mauritanicus. Named Mauriporin, the peptide was found to be composed of 48 residues and circular dichroism analysis revealed the peptide to display a well defined α-helical structure in membrane mimicking environments. A synthetic replicate of Mauriporin was found to exert potent selective cytotoxic and antiproliferative activity against prostate cancer cell lines (IC50 4.4–7.8 μM) when compared with non-tumorigenic cells. In this concentration range, Mauriporin produced also negligible degrees of hemolytic activities against mammalian erythrocytes. Apoptotic studies displayed that Mauriporin is not causing cell death through an apoptotic-mediated pathway but possibly through a necrotic mode of cell death. In conclusion Mauriporin may offer a novel therapeutic strategy in the treatment of prostate cancer considering its significant cytotoxic potency against prostate cancer cells and low toxicity to non-tumorigenic cells.

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References

  • Almaaytah A, Zhou M, Wang L, Chen T, Walker B, Shaw C (2012) Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: biochemical and functional characterization of natural peptides and a single site-substituted analog. Peptides 35:291–299

    Article  PubMed  CAS  Google Scholar 

  • Antonarakis ES, Eisenberger MA (2011) Expanding treatment options for metastatic prostate cancer. N Engl J Med 364:2055–2058

    Article  PubMed  CAS  Google Scholar 

  • Chen T, Folan R, Kwok H, O’Kane EJ, Bjourson AJ, Shaw C (2003) Isolation of scorpion (Androctonus amoreuxi) putative alpha neurotoxins and parallel cloning of their respective cDNAs from a single sample of venom. Regul Pept 115:115–121

    Article  PubMed  CAS  Google Scholar 

  • Chen T, Walker B, Zhou M, Shaw C (2005) Molecular cloning of a novel putative potassium channel-blocking neurotoxin from the venom of the North African scorpion, Androctonus amoreuxi. Peptides 26:731–736

    Article  PubMed  Google Scholar 

  • Corbier C, Krier F, Mulliert G, Vitoux B, Revol-Junelles AM (2001) Biological activities and structural properties of the atypical bacteriocins mesenterocin 52b and leucocin b-ta33a. Appl Environ Microbiol 67:1418–1422

    Article  PubMed  CAS  Google Scholar 

  • Corona M, Bolivar F, Becerril B (2000) Peptides and genes coding for scorpion toxins that affect ion-channels. Biochimie 82:861–868

    Article  PubMed  Google Scholar 

  • Coughlin SS (2008) Surviving cancer or other serious illness: a review of individual and community. Resources 58:60–64

    Google Scholar 

  • Deshane J, Garner CC, Sontheimer H (2003) Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem 278:4135–4144

    Article  PubMed  CAS  Google Scholar 

  • Dobrzynska I, Szachowicz-Petelska B, Sulkowski S, Figaszewski Z (2005) Changes in electric charge and phospholipids composition in human colorectal cancer cells. Mol Cell Biochem 276:113–119

    Article  PubMed  CAS  Google Scholar 

  • D’Suze G, Schwartz EF, García-Gómez BI, Sevcik C, Possani LD (2009) Molecular cloning and nucleotide sequence analysis of genes from a cDNA library of the scorpion Tityus discrepans. Biochimie 91:1010–1019

    Article  PubMed  Google Scholar 

  • Fletcher JI, Haber M, Henderson MJ, Norris MD (2010) ABC transporters in cancer: more than just drug efflux pumps. Nat Rev Cancer 10:147–156

    Article  PubMed  CAS  Google Scholar 

  • Goudet C, Chi CW, Tytgat J (2002) An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon 40:1239–1258

    Article  PubMed  CAS  Google Scholar 

  • Gupta SD, Gomes A, Debnath A, Saha A, Gomes A (2010) Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Chem Biol Interact 183:293–303

    Article  PubMed  Google Scholar 

  • Hoskin DW, Ramamoorthy A (2008) Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta 1778:357–375

    Article  PubMed  CAS  Google Scholar 

  • Huang YB, He LY, Jiang HY, Chen YX (2012) Role of helicity on the anticancer mechanism of action of cationic-helical peptides. Int J Mol Sci 13:6849–6862

    Article  PubMed  CAS  Google Scholar 

  • Ilić N, Novković M, Guida F, Xhindoli D, Benincasa M, Tossi A, Juretić D (2013) Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences. Biochim Biophys Acta 1828:1004–1012

    Article  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A (2010) Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 28:126–131

    Article  PubMed  Google Scholar 

  • Kozminsky-Atias A, Bar-Shalom A, Mishmar D, Zilberberg N (2008) Assembling an arsenal, the scorpion way. BMC Evol Biol 8:333

    Article  PubMed  Google Scholar 

  • Lehmann J, Retz M, Sidhu SS, Suttmann H, Sell M, Paulsen F, Harder J, Unteregger G, Stöckle M (2006) Antitumor activity of the antimicrobial peptide magainin II against bladder cancer cell lines. Eur Urol 50:141–147

    Article  PubMed  CAS  Google Scholar 

  • Leibowitz RL, Tucker SJ (2001) Treatment of localized prostate cancer with intermittent triple androgen blockade: preliminary results in 110 consecutive patients. Oncologist 6:177–182

    Article  PubMed  CAS  Google Scholar 

  • Leuschner C, Hansel W (2004) Membrane disrupting lytic peptides for cancer treatments. Curr Pharm Des 10:2299–2310

    Article  PubMed  CAS  Google Scholar 

  • Mason AJ, Marquette A, Bechinger B (2007) Zwitterionic phospholipids and sterols modulate antimicrobial peptide-induced membrane destabilization. Biophys J 93:4289–4299

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki K, Sugishita K, Fujii N, Miyajima K (1995) Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2. Biochemistry 34:3423–3429

    Article  PubMed  CAS  Google Scholar 

  • Moerman L, Bosteels S, Noppe W, Willems J, Clynen E, Schoofs L, Thevissen K, Tytgat J, Van Eldere J, Van Der Walt J, Verdonck F (2002) Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa. Eur J Biochem 269:4799–4810

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez de la Vega RC, Possani LD (2005) Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 46:831–844

    Article  PubMed  CAS  Google Scholar 

  • Ruiming Z, Yibao M, Yawen H, Zhiyong D, Yingliang W, Zhijian C, Wenxin L (2010) Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components. BMC Genomics 11:452

    Article  PubMed  Google Scholar 

  • Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:528–537

    Article  PubMed  CAS  Google Scholar 

  • Schwartz EF, Diego-Garcia E, Rodriguez de la Vega RC, Possani LD (2007) Transcriptome analysis of the venom gland of the Mexican scorpion Hadrurus gertschi (Arachnida: Scorpiones). BMC Genomics 8:119

    Article  PubMed  Google Scholar 

  • Schweizer F (2009) Cationic amphiphilic peptides with cancer-selective toxicity. Eur J Pharmacol 625:190–194

    Article  PubMed  CAS  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2012) Cancer statistics 2012(62):10–29

    Google Scholar 

  • Wang K, Zhang B, Zhang W, Yan J, Li J, Wang R (2008) Antitumor effects, cell selectivity and structure–activity relationship of a novel antimicrobial peptide polybia-MPI. Peptides 29:963–968

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Li H, Li S, Tian L, Shang D (2012) Antitumor effects and cell selectivity of temporin-1CEa, an antimicrobial peptide from the skin secretions of the Chinese brown frog (Rana chensinensis). Biochimie 94:434–441

    Article  PubMed  CAS  Google Scholar 

  • Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL (2008) Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 148:435–448

    Article  PubMed  Google Scholar 

  • Yoon WH, Park HD, Lim K, Hwang BD (1996) Effect of O-glycosylated mucin on invasion and metastasis of HM7 human colon cancer cells. Biochem Biophys Res Commun 222:694–699

    Article  PubMed  CAS  Google Scholar 

  • Zelefsky MJ, Kuban DA, Levy LB, Potters L, Beyer DC, Blasko JC, Moran BJ, Ciezki JP, Zietman AL, Pisansky TM, Elshaikh M, Horwitz EM (2007) Multi-institutional analysis of long-term outcome for stages T1–T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys 67:327–333

    Article  PubMed  Google Scholar 

  • Zeng XC, Li WX, Peng F, Zhu ZH (2000) Cloning and characterization of a novel cDNA sequence encoding the precursor of a novel venom peptide (BmKbpp) related to a bradykinin-potentiating peptide from Chinese scorpion Buthus martensii Karsch. IUBMB Life 49:207–210

    PubMed  CAS  Google Scholar 

  • Zeng X, Corzo G, Hahin R (2005) Scorpion venom peptides without disulfide bridges. IUBMB Life 57:13–21

    Article  PubMed  CAS  Google Scholar 

  • Zeng X, Wang S, Nie Y, Zhang L, Luo X (2012) Characterization of BmKbpp, a multifunctional peptide from the Chinese scorpion Mesobuthus martensii Karsch: gaining insight into a new mechanism for the functional diversification of scorpion venom peptides. Peptides 33:44–51

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Ammar Almaaytah

  2. Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan

    Shadi Tarazi

  3. Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Nizar Mhaidat & Tareq L. Mukattash

  4. Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Qosay Al-Balas

Authors
  1. Ammar Almaaytah
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  2. Shadi Tarazi
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  3. Nizar Mhaidat
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  4. Qosay Al-Balas
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  5. Tareq L. Mukattash
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Correspondence to Ammar Almaaytah.

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Almaaytah, A., Tarazi, S., Mhaidat, N. et al. Mauriporin, a Novel Cationic α-Helical Peptide with Selective Cytotoxic Activity Against Prostate Cancer Cell Lines from the Venom of the Scorpion Androctonus mauritanicus . Int J Pept Res Ther 19, 281–293 (2013). https://doi.org/10.1007/s10989-013-9350-3

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  • DOI: https://doi.org/10.1007/s10989-013-9350-3

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