Activity of protegrin-1 against mouse Ehrlich ascites carcinoma in vitro and in vivo

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Abstract

Introduction. The problem of multidrug resistance in cancer treatment creates an urgent demand for developing new effective antitumor agents. Due to the unusual mechanism of recognizing and damaging tumor cells, antimicrobial peptides (AMPs) are considered as possible prototypes for designing such therapeutics.

Aim. This work was aimed to compare the antitumor potential of the promising membranolytic AMP protegrin-1 (PG-1) in vitro and in vivo in Ehrlich ascites carcinoma (EAC) mice model.

Methods. We used two variants of the model by inducing a tumor in solid or ascites form. In the first case, the mice were injected with the peptide twice a week for three weeks, and in the second injections were provided every other day for six days. The activity of AMPs against isolated EAC cells in vitro was analyzed using MTT-test.

Results. PG-1 demonstrated high activity against EAC cells in vitro, but had no significant effect on the lifespan of mice bearing solid or ascites form of EAC tumor at the dosing and administration regimens we used. However, treatment with PG-1 caused a decrease in the ascites volume and in the number of cells in the ascites fluid.

Conclusion. PG-1 retains its antitumor properties in vivo, but it may be presumed, that to effectively suppress tumor growth it requires a more frequent and prolonged administration compared with conventional antitumor antibiotics, of which we adopted the administration regimen for PG-1 in this study.

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About the authors

Alena E. Rudel

Institute of Experimental Medicine

Email: alenarudel@gmail.com
ORCID iD: 0000-0001-9738-057X
SPIN-code: 8735-4061

junior researcher of the laboratory of anticancer peptide drugs of the department of general pathology and pathophysiology

Russian Federation, 197022, Saint-Petersburg, Acad. Pavlov Street, 12

Tatiana A. Filatenkova

Institute of Experimental Medicine

Email: lero269@gmail.com
ORCID iD: 0000-0002-6911-7456
SPIN-code: 4198-3636

Research Fellow

Russian Federation, 197022, Saint-Petersburg, Acad. Pavlov Street, 12

Maria S. Zharkova

Institute of Experimental Medicine

Author for correspondence.
Email: manyvel@mail.ru
ORCID iD: 0000-0003-3352-8197
SPIN-code: 3966-6347
Scopus Author ID: 57205430890
ResearcherId: G-4569-2014

PhD in biology, head of the laboratory of anticancer peptide drugs of the department of general pathology and pathophysiology

Russian Federation, 197022, Saint-Petersburg, Acad. Pavlov Street, 12

References

  1. Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020;21(9):3233. doi: 10.3390/ijms21093233
  2. Lin L, Chi J, Yan Y, et al. Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era. Acta Pharm Sin B. 2021;11(9):2609–2644. doi: 10.1016/j.apsb.2021.07.014
  3. Vallabhapurapu SD, Blanco VM, Sulaiman MK, et al. Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium. Oncotarget. 2015;6(33):34375–34388. doi: 10.18632/oncotarget.6045
  4. Kaynak A, Davis HW, Kogan AB, Lee JH, Narmoneva DA, Qi X. Phosphatidylserine: The Unique Dual-Role Biomarker for Cancer Imaging and Therapy. Cancers (Basel). 2022;14(10):2536. doi: 10.3390/cancers14102536
  5. Dobie C, Skropeta D. Insights into the role of sialylation in cancer progression and metastasis. Br J Cancer. 2021;124(1):76–90. doi: 10.1038/s41416-020-01126-7
  6. Qu B, Yuan J, Liu X, Zhang S, Ma X, Lu L. Anticancer activities of natural antimicrobial peptides from animals. Front Microbiol. 2024;14:1321386. doi: 10.3389/fmicb.2023.1321386
  7. Zhong C, Zhang L, Yu L, Huang J, Huang S, Yao Y. A Review for Antimicrobial Peptides with Anticancer Properties: Re-Purposing of Potential Anticancer Agents. BIO Integr. 2020;1:156–167. doi: 10.15212/bioi-2020-0013
  8. Henriques ST, Melo MN, Castanho MA. Cell-penetrating peptides and antimicrobial peptides: how different are they?. Biochem J. 2006;399(1):1–7. doi: 10.1042/BJ20061100
  9. Kokryakov VN, Harwig SS, Panyutich EA, et al. Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett. 1993;327(2):231–236. doi: 10.1016/0014-5793(93)80175-t
  10. Capone R, Mustata M, Jang H, Arce FT, Nussinov R, Lal R. Antimicrobial protegrin-1 forms ion channels: molecular dynamic simulation, atomic force microscopy, and electrical conductance studies. Biophys J. 2010;98(11):2644–2652. doi: 10.1016/j.bpj.2010.02.024
  11. Rothan HA, Mohamed Z, Sasikumar PG, Reddy KA, Rahman NA, Yusof R. In Vitro Characterization of Novel Protegrin-1 Analogues Against Neoplastic Cells. Int J Pept Res Ther. 2014;20:259–267. doi: 10.1007/s10989-013-9388-2
  12. Niu M, Chai S, You X, et al. Expression of porcine protegrin-1 in Pichia pastoris and its anticancer activity in vitro. Exp Ther Med. 2015;9(3):1075–1079. doi: 10.3892/etm.2015.2202
  13. Chernov AN, Kim AV, Skliar SS, et al. Expression of molecular markers and synergistic anticancer effects of chemotherapy with antimicrobial peptides on glioblastoma cells. Cancer Chemother Pharmacol. 2024;93(5):455–469. doi: 10.1007/s00280-023-04622-8
  14. Chernov AN, Orlov DS, Shamova OV. Peptides of the innate immunity as potential anticancer agents: pros and cons. Medical Immunology (Russia). 2021;23(6):1285–1306. (In Russ). doi: 10.15789/1563-0625-POT-2303
  15. Shamova OV, Sakuta GA, Orlov DS, et al. Effects of antimicrobial peptides of neutrophils on tumor and normal host cells in culture. Cell Tissue Biol. 2007;1:524–533. doi: 10.1134/S1990519X07060090
  16. Kopeikin PM, Zharkova MS, Kolobov AA, et al. Caprine Bactenecins as Promising Tools for Developing New Antimicrobial and Antitumor Drugs. Front Cell Infect Microbiol. 2020;10:552905. doi: 10.3389/fcimb.2020.552905
  17. Menchinskaya E, Gorpenchenko T, Silchenko A, Avilov S, Aminin D. Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A2-2. Mar Drugs. 2019;17(11):597. doi: 10.3390/md17110597
  18. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63. doi: 10.1016/0022-1759(83)90303-4
  19. Shamova OV, Sakuta GA, Orlov DS, et al. Antitumor activity of the cationic antimicrobial peptide from porcine neutrophils protegrin-1 and its synthetic analogues. Advances in current natural sciences. 2004;(3):44–46. (In Russ).
  20. Harwig SS, Waring A, Yang HJ, Cho Y, Tan L, Lehrer RI. Intramolecular disulfide bonds enhance the antimicrobial and lytic activities of protegrins at physiological sodium chloride concentrations. Eur J Biochem. 1996;240(2):352–357. doi: 10.1111/j.1432-1033.1996.0352h.x
  21. Steinstraesser L, Klein RD, Aminlari A, et al. Protegrin-1 enhances bacterial killing in thermally injured skin. Crit Care Med. 2001;29(7):1431–1437. doi: 10.1097/00003246-200107000-00022
  22. Brechbill AM, Moyer TB, Parsley NC, Hicks LM. Creating optimized peptide libraries for AMP discovery via PepSAVI-MS. Methods Enzymol. 2022;663:41–66. doi: 10.1016/bs.mie.2021.10.024
  23. Xia LJ, Wu YL, Ma J, Zhang FC. Therapeutic effects of antimicrobial peptide on malignant ascites in a mouse model. Mol Med Rep. 2018;17(5):6245–6252. doi: 10.3892/mmr.2018.8691
  24. Salem ML, Shoukry NM, Teleb WK, Abdel-Daim MM, Abdel-Rahman MA. In vitro and in vivo antitumor effects of the Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich ascites tumor model. Springerplus. 2016;5:570. doi: 10.1186/s40064-016-2269-3
  25. Dhanyamraju PK, Schell TD, Amin S, Robertson GP. Drug-Tolerant Persister Cells in Cancer Therapy Resistance. Cancer Res. 2022;82(14):2503–2514. doi: 10.1158/0008-5472.CAN-21-3844

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