The membrane effects of melittin on gastric and colorectal cancer

English version

Autoři: Caroline Soliman ^aff001; Sarah Eastwood ^aff001; Vi Khanh Truong ^aff001; Paul A. Ramsland ^aff001; Aaron Elbourne ^aff001
Působiště autorů: School of Science, RMIT University, Bundoora West Campusm Bundoora, Victoria, Australia ^aff001; Nanobiotechnology Laboratory, RMIT University, Melbourne City Campus, Melbourne, Victoria, Australia ^aff002; Department of Immunology, Central Clinical School (Monash University), Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia ^aff003; Department of Surgery Austin Health (University of Melbourne), Austin Health, Heidelberg, Victoria, Australia ^aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224028

Souhrn

The cytotoxic effects of melittin, a bee-venom peptide, have been widely studied towards cancer cells. Typically, these studies have examined the effect of melittin over extended-time courses (6–24 hours), meaning that immediate cellular interactions have been overlooked. In this work, we demonstrate the rapid effects of melittin on both gastric and colorectal cancer, specifically AGS, COLO205 and HCT-15 cell lines, over a period of 15 minutes. Melittin exhibited a dose dependent effect at 4 hours of treatment, with complete cellular death occurring at the highest dose of 20 μg/mL. Interestingly, when observed at shorter time points, melittin induced cellular changes within seconds; membrane damage was observed as swelling, breakage or blebbing. High-resolution imaging revealed treated cells to be compromised, showing clear change in cellular morphology. After 1 minute of melittin treatment, membrane changes were observed, and intracellular material could be seen expelled from the cells. Overall, these results enhance our understanding of the fast acting anti-cancer effects of melittin.

Klíčová slova:

Apoptosis – Cancer treatment – Cell death – Cell membranes – Cell staining – Colorectal cancer – Scanning electron microscopy – Membrane staining

Zdroje

1. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018 [press release]. 12 September 2018 2018.

2. Wang S, Jia M. Antibody Therapies in Cancer. In: Zhang S, editor. Progress in Cancer Immunotherapy. Dordrecht: Springer Netherlands; 2016. p. 1–67.

3. Yavari B, Mahjub R, Saidijam M, Raigani M, Soleimani M. The Potential Use of Peptides in Cancer Treatment. Curr Protein Peptide Sci. 2018;19(8):759–70.

4. Marqus S, Pirogova E, Piva TJ. Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci. 2017;24(1):21–36. doi: 10.1186/s12929-017-0328-x 28320393

5. Liu C-c, Hao D-j, Zhang Q, An J, Zhao J-j, Chen B, et al. Application of bee venom and its main constituent melittin for cancer treatment. Cancer Chemother Pharmacol. 2016;78(6):1113–30. doi: 10.1007/s00280-016-3160-1 27677623

6. Rady I, Siddiqui I, Rady M, Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Lett. 2017;402:16–31. doi: 10.1016/j.canlet.2017.05.010 28536009

7. Premratanachai P, Chanchao C. Review of the anticancer activities of bee products. Asian Pacific Journal of Tropical Biomedicine. 2014;4(5):337–44. doi: 10.12980/APJTB.4.2014C1262 25182716

8. Choi JH, Jang AY, Lin S, Lim S, Kim D, Park K, et al. Melittin, a honeybee venom-derived antimicrobial peptide, may target methicillin-resistant Staphylococcus aureus. Mol Med Report. 2015;12(5):6483–90.

9. Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB, et al. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol. 2012;258(1):72–81. doi: 10.1016/j.taap.2011.10.009 22027265

10. Kong G-M, Tao W-H, Diao Y-L, Fang P-H, Wang J-J, Bo P, et al. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway. World J Gastroenterol. 2016;22(11):3186–95. doi: 10.3748/wjg.v22.i11.3186 27003995

11. Mahmoodzadeh A, Zarrinnahad H, Bagheri KP, Moradia A, Shahbazzadeh D. First report on the isolation of melittin from Iranian honey bee venom and evaluation of its toxicity on gastric cancer AGS cells. J Chin Med Assoc. 2015;78(10):574–83. doi: 10.1016/j.jcma.2015.06.008 26316200

12. Mularski A, Wilksch JJ, Wang H, Hossain MA, Wade JD, Separovic F, et al. Atomic Force Microscopy Reveals the Mechanobiology of Lytic Peptide Action on Bacteria. Langmuir: the ACS journal of surfaces and colloids. 2015;31(22):6164–71.

13. Rajabnejad SH, Mokhtarzadeh A, Abnous K, Taghdisi SM, Ramezani M, Razavi BM. Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer. Drug Dev Ind Pharm. 2018;44(6):982–7. doi: 10.1080/03639045.2018.1427760 29325460

14. Zarrinnahad H, Mahmoodzadeh A, Hamidi M, Mahdavi M, Moradi A, Bagheri K, et al. Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line. Int J Pept Res Ther. 2018;24(4):563–70. doi: 10.1007/s10989-017-9641-1 30416405

15. Zhang S-F, Chen Z. Melittin exerts an antitumor effect on non-small cell lung cancer cells. Mol Med Report. 2017;16(3):3581–6.

16. Tipgomut C, Wongprommoon A, Takeo E, Ittiudomrak T, Puthong S, Chanchao C. Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages. Asian Pac J Cancer Prev. 2018;19(12):3427–34. doi: 10.31557/APJCP.2018.19.12.3427 30583665

17. Giménez D, Sánchez-Muñoz OL, Salgado J. Direct observation of nanometer-scale pores of melittin in supported lipid monolayers. Langmuir: the ACS journal of surfaces and colloids. 2015;31(10):3146–58.

18. Tosteson M, Holmes S, Razin M, Tosteson D. Melittin lysis of red cells. An International Journal for Studies on the Structure, Function, and Genesis of Biomembranes. 1985;87(1):35–44.

19. DeGrado WF, Musso GF, Lieber M, Kaiser ET, Kezdy FJ. Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys J. 1982;37(1):329–38. doi: 10.1016/S0006-3495(82)84681-X 7055625

20. Bei C, Bindu T, Remant KC, Peisheng X. Dual secured nano-melittin for the safe and effective eradication of cancer cells. J Mater Chem B. 2014;3(1):25–9. doi: 10.1039/C4TB01401D 25734006

21. Ling CQ, Li B, Zhang C, Zhu DZ, Huang XQ, Gu W, et al. Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann Oncol. 2005;16(1):109–15. doi: 10.1093/annonc/mdi019 15598947

22. Qian C-Y, Wang K-L, Fang F-F, Gu W, Huang F, Wang F-Z, et al. Triple-controlled oncolytic adenovirus expressing melittin to exert inhibitory efficacy on hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8(9):10403. 26617748

23. Sun D, Sun M, Zhu W, Wang Z, Li Y, Ma J. The anti-cancer potency and mechanism of a novel tumor-activated fused toxin, DLM. Toxins (Basel). 2015;7(2):423. doi: 10.3390/toxins7020423 25658509

24. Wang D, Hu L, Su M, Wang J, Xu T. Preparation and functional characterization of human vascular endothelial growth factor-melittin fusion protein with analysis of the antitumor activity in vitro and in vivo. Int J Oncol. 2015;47(3):1160. doi: 10.3892/ijo.2015.3078 26166416

25. Zhao H, Feng X, Han W, Diao Y, Han D, Tian X, et al. Enhanced binding to and killing of hepatocellular carcinoma cells in vitro by melittin when linked with a novel targeting peptide screened from phage display. Journal of Peptide Science. 2013;19(10):639–50. doi: 10.1002/psc.2542 24014474

26. Dufrêne YF, Ando T, Garcia R, Alsteens D, Martinez-Martin D, Engel A, et al. Imaging modes of atomic force microscopy for application in molecular and cell biology. Nature Nanotechnology. 2017;12(4):295–307. doi: 10.1038/nnano.2017.45 28383040

27. Müller DJ, Dufrêne YF. Atomic force microscopy: a nanoscopic window on the cell surface. Trends Cell Biol. 2011;21(8):461–9. doi: 10.1016/j.tcb.2011.04.008 21664134

28. Parot P, Dufrêne YF, Hinterdorfer P, Le Grimellec C, Navajas D, Pellequer J-L, et al. Past, present and future of atomic force microscopy in life sciences and medicine. J Mol Recognit. 2007;20(6):418–31. doi: 10.1002/jmr.857 18080995

29. Nečas D, Klapetek P. Gwyddion: an open-source software for SPM data analysis. Central European Journal of Physics. 2012;10(1):181–8.

30. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495–516. doi: 10.1080/01926230701320337 17562483

31. Wlodkowic D, Skommer J, Darzynkiewicz Z. Flow cytometry-based apoptosis detection. Methods Mol Biol. 2009;559:19–32. doi: 10.1007/978-1-60327-017-5_2 19609746

32. Barranco SC, Townsend CM Jr., Casartelli C, Macik BG, Burger NL, Boerwinkle WR, et al. Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res. 1983;43(4):1703–9. 6831414

33. Walsh EG, Maher S, Devocelle M, O'Brien PJ, Baird AW, Brayden DJ. High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs. Peptides. 2011;32(8):1764–73. doi: 10.1016/j.peptides.2011.06.006 21703316

34. Lee M-T, Sun T-L, Hung W-C, Huang HW. Process of inducing pores in membranes by melittin. Proc Natl Acad Sci USA. 2013;110(35):14243. doi: 10.1073/pnas.1307010110 23940362

35. Weston KM, Alsalami M, Raison RL. Cell membrane changes induced by the cytolytic peptide, melittin, are detectable by 90 degrees laser scatter. Cytometry. 1994;15(2):141–7. doi: 10.1002/cyto.990150207 8168400

36. Dempsey CE. The actions of melittin on membranes. BBA—Reviews on Biomembranes. 1990;1031(2):143–61. doi: 10.1016/0304-4157(90)90006-x 2187536

37. Oršolić N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012;31(1):173–94.

38. Tosteson MT, Tosteson DC. The sting. Melittin forms channels in lipid bilayers. Biophys J. 1981;36(1):109–16. doi: 10.1016/S0006-3495(81)84719-4 6269667

39. Gajski G, Garaj-Vrhovac V. Melittin: A lytic peptide with anticancer properties. Environ Toxicol Pharmacol. 2013;36(2):697–705. doi: 10.1016/j.etap.2013.06.009 23892471

40. Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007;115(2):246–70. doi: 10.1016/j.pharmthera.2007.04.004 17555825

41. Mihajlovic M, Lazaridis T. Antimicrobial peptides in toroidal and cylindrical pores. BBA—Biomembranes. 2010;1798(8):1485–93. doi: 10.1016/j.bbamem.2010.04.004 20403332

42. Hanke W, Methfessel C, Wilmsen H-U, Katz E, Jung G, Boheim G. Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores. BBA—Biomembranes. 1983;727(1):108–14. doi: 10.1016/0005-2736(83)90374-7 6824646

43. Liu J, Xiao S, Li J, Yuan B, Yang K, Ma Y. Molecular details on the intermediate states of melittin action on a cell membrane. BBA—Biomembranes. 2018;1860(11):2234–41. doi: 10.1016/j.bbamem.2018.09.007 30409519

44. Ramirez L, Shekhtman A, Pande J. Nuclear Magnetic Resonance-Based Structural Characterization and Backbone Dynamics of Recombinant Bee Venom Melittin. Biochemistry. 2018;57(19):2775. doi: 10.1021/acs.biochem.8b00156 29668274

45. Sun D, Forsman J, Woodward CE. Multistep Molecular Dynamics Simulations Identify the Highly Cooperative Activity of Melittin in Recognizing and Stabilizing Membrane Pores. Langmuir: the ACS journal of surfaces and colloids. 2015;31(34):9388–401.

46. Ladokhin AS, Selsted ME, White SH. Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: pore formation by melittin. Biophys J. 1997;72(4):1762–6. doi: 10.1016/S0006-3495(97)78822-2 9083680

47. Khawar IA, Kim JH, Kuh H-J. Improving drug delivery to solid tumors: Priming the tumor microenvironment. J Controlled Release. 2015;201:78–89.

48. Tannock IF, Lee CM, Tunggal JK, Cowan DSM, Egorin MJ. Limited Penetration of Anticancer Drugs through Tumor Tissue. Clin Cancer Res. 2002;8(3):878–84. 11895922

49. Hou KK, Pan H, Ratner L, Schlesinger PH, Wickline SA. Mechanisms of Nanoparticle-Mediated siRNA Transfection by Melittin-Derived Peptides. ACS Nano. 2013;7(10):8605–15. doi: 10.1021/nn403311c 24053333

50. Pan H, Soman NR, Schlesinger PH, Lanza GM, Wickline SA. Cytolytic peptide nanoparticles (‘NanoBees’) for cancer therapy. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2011;3(3):318–27. doi: 10.1002/wnan.126 21225660

51. Soman NR, Baldwin SL, Hu G, Marsh JN, Lanza GM, Heuser JE, et al. Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth. The Journal of Clinical Investigation. 2009;119(9):2830–42. doi: 10.1172/JCI38842 19726870

The membrane effects of melittin on gastric and colorectal cancer

Souhrn

Klíčová slova:

Zdroje

PLOS One

INSIGHTS from European Respiratory Congress

Současné pohledy na riziko v parodontologii

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií

Střevní příprava před kolonoskopií