TY - JOUR T1 - Investigation the Cytotoxic and Anti-Proliferative Effects of Crude Venom of Euscorpius mingrelicus (Scorpiones: Euscorpiidae) Scorpion AU - Yiğit Kayhan, Nazife AU - Çorak Öcal, İlkay AU - Akdeniz, Mustafa PY - 2022 DA - December DO - 10.26650/EurJBiol.2022.1105838 JF - European Journal of Biology JO - Eur J Biol PB - Istanbul University WT - DergiPark SN - 2602-2575 SP - 117 EP - 124 VL - 81 IS - 2 LA - en AB - 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. KW - Scorpion Venom KW - Cancer KW - Anti-Proliferative KW - Apoptosis KW - Necrosis CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 7. Park J, Cho SY, Choi SJ. Purification and characterization of hepatic lipase from Todarodes pacificus. BMB reports 2008; 41: 254-8. google scholar CR - 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 CR - 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 CR - 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 CR - 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 CR - 12. du Plessis JL. Collection of venom from southern African scorpi-ons. Toxicon 2005; 45: 681-2. google scholar CR - 13. Diniz CR. Chemical and pharmacological aspects of Tityinae ven-oms. Arthropod venoms. Berlin: Springer-Verlag, 1978, 379-94. google scholar CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 19. Ammar A, Qosay A. Scorpion venom peptides with no disulfide bridges: A review. Peptides 2014; 51: 35-45. google scholar CR - 20. Yu FH, Catterall WA. Overview of the voltage-gated sodium chan-nel family. Genome Biol 2003; 4(3): 1-7. google scholar CR - 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 CR - 22. Cestele S, Catterall WA. Molecular mechanisms of neurotoxin ac-tion on voltage-gated sodium channels. Biochimie 2000; 82(9): 883-92. google scholar CR - 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 CR - 24. Catterall WA. Cellular and molecular biology of voltage-gated so-dium channels. Physiol Rev 1992; 72(4): 15-48. google scholar CR - 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 CR - 26. Tossi A, Sandri L, Giangaspero A. Amphipathic, a-helical antimicro-bial peptides. Biopolymers 2000; 55: 4-30. google scholar CR - 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 CR - 28. Kelle I. Terapötik potansiyele sahip venom peptidleri. Dicle Med J 2006; 33: 113 - 26. google scholar CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 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 CR - 37. Hayden MS, West AP, Ghosh S. NF-kappaB and the immune re-sponse. Oncogene 2006; 25: 6758-80. google scholar CR - 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 CR - 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 CR - 40. Sariego J. Breast cancer in the young patient. Am Surg 2010; 76:1397-401. google scholar CR - 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 CR - 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 UR - https://doi.org/10.26650/EurJBiol.2022.1105838 L1 - https://dergipark.org.tr/en/download/article-file/2383804 ER -