Investigation the Cytotoxic and Anti-Proliferative Effects of Crude Venom of Euscorpius mingrelicus (Scorpiones: Euscorpiidae) Scorpion

Year 2022, , 117 - 124, 29.12.2022

Nazife Yiğit Kayhan , İlkay Çorak Öcal , Mustafa Akdeniz

https://doi.org/10.26650/EurJBiol.2022.1105838

Abstract

Objective: Since they contain various toxins that may influence various biological events, scorpion venoms raise new hopes for cancer treatments. It is thought that the bioactive compounds contained in scorpion venom could be used in cancer treatments in near future. Materials and Methods: In this study, different cytotoxic, apoptotic, necrotic, and anti-proliferative effects of crude venom obtained from Euscorpius mingrelicus (Kessler, 1874) scorpions species were tested on human breast cancer cells (MCF-7), human lung carcinoma cells (H1299), and mice fibroblast cells (L929). Results: It was determined that the crude venom had cytotoxic and anti-proliferative effects on MCF-7 and fibroblast cells even when at low concentrations and the effect on H1299 was half of the effect on MCF-7 and fibroblast. It was observed that, as the dilution rate increased, the venom effect decreased, apoptosis and necrosis rates on H1299 decreased, and it had no effect on cell proliferation. With regards to the MCF-7 cells, apoptosis and necrosis rates were similar in H1299 cells. Conclusion: It was found that crude venom of E. mingrelicus scorpion played an effective role in decreasing the proliferation of MCF-7 cells, and more comprehensive studies are needed in order to determine the toxin that is responsible for this effect.

Keywords

Scorpion Venom, Cancer, Anti-Proliferative, Apoptosis, Necrosis

References

• 1 Lipps BV Novel snake venom protein cytolytic to cancer cells in vitro and in vivo systems J Venom Anim Toxins 1999; 5: 172-83 google scholar
• 2 Szakacs G, Paterson JK, Ludwig JA, Genthe CB, Gottesman MM Tar-geting multidrug resistance in Cancer Nat Rev Drug Discov 2006; 5: 219-34 google scholar
• 3 Kocdogan K Meme Kanserli Hastalarda Glutatyon S-Trensferaz Izozim-lerin Coklu Ilaç Direnç Mekanizmasındaki Proteinlerle Olan Ilişkilerin Incelenmesi K Ü Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi 2016 google scholar
• 4 Cheng D, Dattaro JA, Yakobi R, Bush SP, Gerardo CJ Scorpion en-venomation Medscape 2011 Sep Available from: URL: http:// emedicine medscape com/ article/168230-overview google scholar
• 5 Ozkan O, Carhan A The neutralizing capacity of Androctonus cras-sicauda antivenom against Mesobuthus eupeus scorpion venom Toxicon 2008; 52: 375-9 google scholar
• 6 Gurevitz M, Karbat I, Cohen L, Ilan N, Kahn R, Turkov M, Stankiewicz, M, Stühmer W, Dong K, Gordon D The insecticidal potential of scorpion 0-toxins .Toxicon 2007; 49:473-89. google scholar
• 7. Park J, Cho SY, Choi SJ. Purification and characterization of hepatic lipase from Todarodes pacificus. BMB reports 2008; 41: 254-8. google scholar
• 8. Raposo C. Scorpion and spider venoms in cancer treatment: state of the art, challenges, and perspectives. J Clin Transl Res 2017; 24: 233-49. google scholar
• 9. Gopalakrishnakone P, Cheah J, Gwee MCE. Black scorpion (Het-erometrus longimanus) as a laboratory animal: maintenance of a colony of scorpion for milking of venom for research, using a re-straining device. Lab Anim 1995; 29: 456-8. google scholar
• 10. Oukkache N, Chgoury F, Lalaoui M, Cano A A, Ghalim N. Compari-son between two methods of scorpion venom milking in Morocco. J Venom Anim Toxins Incl Trop Dis 2013; 19: 5-8. google scholar
• 11. Tobassum S, Tahir HM, Zahid MT, Gardner QA, Ahsan MM. Effect of milking method, diet, and temperature on venom production in scorpions. J Insect Sci 2018; 18: 19-21. google scholar
• 12. du Plessis JL. Collection of venom from southern African scorpi-ons. Toxicon 2005; 45: 681-2. google scholar
• 13. Diniz CR. Chemical and pharmacological aspects of Tityinae ven-oms. Arthropod venoms. Berlin: Springer-Verlag, 1978, 379-94. google scholar
• 14. Willems J, Noppe W, Moerman L, Van der WJ, Verdonck F. Cationic peptides from scorpion venom can stimulate and inhibit polymor-phonuclear granulocytes. Toxicon 2002; 40: 1679-83. google scholar
• 15. Xiong Y, Lan Z, Wang M, Liu B, Liu X, Fei H, et al. Molecular charac-terization of new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensii Karsch. Toxicon 1999; 37: 1165-80. google scholar
• 16. Mortari MR, Cunha AOS, Ferreira LB, Ferreira dos Santos W. Neuro-toxins from invertebrates as anticonvulsants: From basic research to therapeutic application. Pharmacol Ther 2007; 114: 171-83. google scholar
• 17. Chen Y, Cao L, Zhong M, Zhang Y, Han C, Li Q, et al. Anti-HIV-1 activ-ity of a new scorpion venom peptide derivative Kn2-7. PLoS One 2012; 7: e34947. google scholar
• 18. Zhijian C, Feng L, Yingliang W, Xin M, Wenxin L. Genetic mechanisms of scorpion venom peptide diversification. Toxicon 2006; 47: 348-55. google scholar
• 19. Ammar A, Qosay A. Scorpion venom peptides with no disulfide bridges: A review. Peptides 2014; 51: 35-45. google scholar
• 20. Yu FH, Catterall WA. Overview of the voltage-gated sodium chan-nel family. Genome Biol 2003; 4(3): 1-7. google scholar
• 21. Possani LD, Merino E, Corona M, Bolivar F, Becerril B. Peptides and genes coding for scorpion toxins that affect ion-channels. Bio-chimie 2000; 82(9): 861-8. google scholar
• 22. Cestele S, Catterall WA. Molecular mechanisms of neurotoxin ac-tion on voltage-gated sodium channels. Biochimie 2000; 82(9): 883-92. google scholar
• 23. Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M. Potassium channels: molecular defects, diseases, and therapeutic opportuni-ties. Pharmacol Rev 2000; 52 (4): 557-94. google scholar
• 24. Catterall WA. Cellular and molecular biology of voltage-gated so-dium channels. Physiol Rev 1992; 72(4): 15-48. google scholar
• 25. Cid-Uribe JI, Veytia-Bucheli JI, Romero-Gutierrez T, Ortiz E, Possani LD. Scorpion venomics: a 2019 overview. Expert Rev Proteomics 2020; 7(1): 67-83. google scholar
• 26. Tossi A, Sandri L, Giangaspero A. Amphipathic, a-helical antimicro-bial peptides. Biopolymers 2000; 55: 4-30. google scholar
• 27. Bradford MM. Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of pro-tein-dye binding. Anal Biochem 1976; 72: 248-54. google scholar
• 28. Kelle I. Terapötik potansiyele sahip venom peptidleri. Dicle Med J 2006; 33: 113 - 26. google scholar
• 29. Çalışkan F, Sivas H, Şahin Y. Purification of Ac8, Ac9 and Ac10 peptıdes from Androctonus crassicauda crude venom with cyto-toxic effect on Bc3h1 cells. Anadolu Univ J of Sci and Technology -A-Appl Sciand Eng 2009;10(2):515-24. google scholar
• 30. Omran MAA. Cytotoxic and apoptotic effects of scorpion Leiurus quinquestriatus venom on 293T and C2C12 eukaryotic cell lines. J Venom Anim Toxins Incl Trop Dis 2003; 9:255-76. google scholar
• 31. Fu YJ, Yin LT, Liang AH, Zhang CF, Wang W, Chai BF, et al. Therapeu-tic potential of chlorotoxin-like neurotoxin from the Chinese scor-pion for human gliomas. Neurosci Lett 2007; 412 (1): 62-7. google scholar
• 32. Veiseh M, Gabikian P, Bahrami SB. Tumor paint: a cholorotoxin: L Cy5.5 bioconjugate for interaoperative visualization of cancer foci. Cancer Research 2007; 67: 6882-8. google scholar
• 33. Kesavan K, Ratliff J, Johnson EW, Dahlberg W, Asara JM, Misra P. Annexin A2 is a molecular target for TM601, a peptide with tu-mor-targeting and anti-angiogenic effects. J Biol Chem 2010; 285: 4366-74. google scholar
• 34. Sun C, Stephen Z, Veiseh O, Harisen S, Lee D, Ellenbogen RG, et al. Tumor targeted drug delivery and MRI contrast enhancement by chlorotoxin conjugated iron oxide nanoparticle. Nanomed 2008; 3: 495-505. google scholar
• 35. Wang WX, Ji YH. Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro. J Neuro-Oncol 2005; 73(1): 1-7. google scholar
• 36. Gupta SD, Gomes A, Debnath A, Saha A, Gomes A. Apoptosis in-duction in human leukemic cells by a novel protein bengalin, iso-lated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Chem Biol Interact 2010; 183(2): 293-303. google scholar
• 37. Hayden MS, West AP, Ghosh S. NF-kappaB and the immune re-sponse. Oncogene 2006; 25: 6758-80. google scholar
• 38. Zhang YY, Wu LC, Wang ZP, Wang ZX, Jia Q, Jiang GS, et al. Anti-pro-liferation effect of polypeptide extracted from scorpion venom on human prostate cancer cells in vitro. J Clin Med Res 2009; 1(1): 24-3. google scholar
• 39. Feng L, Gao R, Gopalakrishnakone P. Isolation and characterization of a hyaluronidase from the venom of Chinese red scorpion Buthus martensi. Comp Biochem Physiol C Toxicol Pharmacol 2008; 148: 250-7. google scholar
• 40. Sariego J. Breast cancer in the young patient. Am Surg 2010; 76:1397-401. google scholar
• 41. Pessini AC, Takao TT, Cavalheiro EC, Vichnewski W, Sampaio SV, Giglio JR, et al. A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids. Toxicon 2001; 39: 1495-504. google scholar
• 42. Norberg E, Orrenius S, Zhivotovsky B. Mitochondrial regulation of cell death: Processing of apoptosis-inducing factor (AIF). Biochem Biophy Res Comm 2010; 396: 95-100. google scholar