Exploring snake venom-derived molecules for cancer treatment: challenges and opportunities

Divya Ramesh Shankar M. Bakkannavar Gautam Kumar Vinutha R. Bhat   

Open Access   

Published:  May 12, 2025

DOI: 10.7324/JAPS.2025.220739
Abstract

Cancer is one of the leading causes of premature death worldwide. Conventional treatment strategies available for cancer have side effects varying from minor to life-threatening conditions. Hence, alternative treatment strategies have been proposed for the management of cancer. Natural agents such as snake venom have been proven effective in treating different malignancies. Snake venoms contain many bioactive components that have promising anticancer properties. The following review highlights the various snake venom components and their potential as novel anticancer agents. We explored the mechanisms of action, cytotoxic effects, and apoptosis-inducing capabilities of these bioactive molecules against different cancer cell lines. Additionally, we discuss the challenges and opportunities in translating snake venom-based therapies into clinical applications. Through an analysis of the latest research findings, this review highlights the therapeutic ability of snake venom components against malignant cells and encourages further investigations in this field.


Keyword:     Snake venom components anticancer properties nanoparticles extracellular vesicles therapeutic potential


Citation:

Ramesh D, Bakkannavar SM, Kumar G, Bhat VR. Exploring snake venom-derived molecules for cancer treatment: challenges and opportunities. J Appl Pharm Sci. 2025. Online First. http://doi.org/10.7324/JAPS.2025.220739

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

1. Utkin YN. Animal venom studies: Current benefits and future developments. World J Biol Chem. 2015;6(2):28. https://doi.org/10.4331/wjbc.v6.i2.28

2. Munawar A, Ali SA, Akrem A, Betzel C. Snake venom peptides: tools of biodiscovery. Toxins (Basel). 2018;10(11):474. https://doi.org/10.3390/toxins10110474

3. Undheim EAB, Georgieva DN, Thoen HH, Norman JA, Mork J, Betzel C, et al. Venom on ice: first insights into Antarctic octopus venoms. Toxicon. 2010 Nov;56(6):897-913. https://doi.org/10.1016/j.toxicon.2010.06.013

4. King GF. Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin Biol Ther. 2011 Nov;11(11):1469- 84. https://doi.org/10.1517/14712598.2011.621940

5. Ruder T, Ali SA, Ormerod K, Brust A, Roymanchadi ML, Ventura S, et al. Functional characterization on invertebrate and vertebrate tissues of tachykinin peptides from octopus venoms. Peptides (NY). 2013;47:71-6. https://doi.org/10.1016/j.peptides.2013.07.002

6. Dutertre S, Jin AH, Vetter I, Hamilton B, Sunagar K, Lavergne V, et al. Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014;5:3521. https://doi.org/10.1038/ncomms4521

7. Koh CY, Kini RM. From snake venom toxins to therapeutics-- cardiovascular examples. Toxicon. 2012 ;59(4):497-506. https://doi.org/10.1016/j.toxicon.2011.03.017

8. Simoes-Silva R, Alfonso J, Gomez A, Holanda RJ, Sobrinho JC, Zaqueo KD, et al. Snake venom, a natural library of new potential therapeutic molecules: challenges and current perspectives. Curr Pharm Biotechnol. 2018 Jun 21;19(4):308-35. https://doi.org/10.2174/1389201019666180620111025

9. Otvos RA, Heus F, Vonk FJ, Halff J, Bruyneel B, Paliukhovich I, et al. Analytical workflow for rapid screening and purification of bioactives from venom proteomes. Toxicon. 2013 Dec 15;76:270-81. https://doi.org/10.1016/j.toxicon.2013.10.013

10. Liu S, Yang F, Zhang Q, Sun MZ, Gao Y, Shao S. "Anatomical" view of the protein composition and protein characteristics for gloydius shedaoensis snake venom via proteomics approach. Anat Record. 2011 ;294(2):273-82. https://doi.org/10.1002/ar.21322

11. Georgieva D, Arni RK, Betzel C. Proteome analysis of snake venom toxins: pharmacological insights. Expert Rev Proteomics. 2014 Dec;5(6):787-97. https://doi.org/10.1586/14789450.5.6.787

12. Ediss.sub.hamburg. Analysis of the low molecular weight peptides of selected snake venoms. [cited 2022 Jul 28]. Available from: https:// ediss.sub.uni-hamburg.de/handle/ediss/4696

13. Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug Discov 2003;2(10):790-802. https://doi.org/10.1038/nrd1197

14. Tu AT. Overview of snake venom chemistry. Adv Exp Med Biol. 1996;391:37-62. https://doi.org/10.1007/978-1-4613-0361-9_3

15. Oliveira AL, Viegas MF, da Silva SL, Soares AM, Ramos MJ, Fernandes PA. The chemistry of snake venom and its medicinal potential. Nat Rev Chem. 2022;6(7):451-69. https://doi.org/10.1038/s41570-022-00393-7

16. Gutiérrez JM, Lomonte B. Phospholipases A2: unveiling the secrets of a functionally versatile group of snake venom toxins. Toxicon. 2013 Feb 1;62:27-39. https://doi.org/10.1016/j.toxicon.2012.09.006

17. Kini RM, Koh CY. Snake venom three-finger toxins and their potential in drug development targeting cardiovascular diseases. Biochem Pharmacol. 2020 Nov 1;181:114105. https://doi.org/10.1016/j.bcp.2020.114105

18. Kang TS, Georgieva D, Genov N, Murakami MT, Sinha M, Kumar RP, et al. Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis. FEBS J. 2011 Dec 1;278(23):4544-76. https://doi.org/10.1111/j.1742-4658.2011.08115.x

19. Ullah A, Masood R, Ali I, Ullah K, Ali H, Akbar H, et al. Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action. Int J Biol Macromol. 2018 Jul 15;114:788- 811. https://doi.org/10.1016/j.ijbiomac.2018.03.164

20. Hiu JJ, Yap MKK. Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase. Biochem Soc Trans. 2020 Apr 29;48(2):719-31. https://doi.org/10.1042/BST20200110

21. Tan KK, Bay BH, Gopalakrishnakone P. L-amino acid oxidase from snake venom and its anticancer potential. Toxicon. 2018 Mar 15;144:7-13. https://doi.org/10.1016/j.toxicon.2018.01.015

22. Arlinghaus FT, Eble JA. C-type lectin-like proteins from snake venoms. Toxicon. 2012 Sep 15;60(4):512-9. https://doi.org/10.1016/j.toxicon.2012.03.001

23. Morita T. Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities. Toxicon. 2005 Jun 15;45(8):1099-114. https://doi.org/10.1016/j.toxicon.2005.02.021

24. Lu Q, Navdaev A, Clemetson JM, Clemetson KJ. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon. 2005 Jun 15;45(8):1089-98. https://doi.org/10.1016/j.toxicon.2005.02.022

25. Vink S, Jin AH, Poth KJ, Head GA, Alewood PF. Natriuretic peptide drug leads from snake venom. Toxicon. 2012 Mar 15;59(4):434-45. https://doi.org/10.1016/j.toxicon.2010.12.001

26. Sridharan S, Kini RM, Richards AM. Venom natriuretic peptides guide the design of heart failure therapeutics. Pharmacol Res. 2020 May 1;155:104687. https://doi.org/10.1016/j.phrs.2020.104687

27. Six DA, Dennis EA. The expanding superfamily of phospholipase A2 enzymes: classification and characterization. Biochim Biophys Acta (BBA). 2000 Oct 31;1488(1-2):1-19. https://doi.org/10.1016/S1388-1981(00)00105-0

28. Burke JE, Dennis EA. Phospholipase A2 structure/function, mechanism, and signaling. J Lipid Res. 2009 Apr ;50(Suppl):S237. https://doi.org/10.1194/jlr.R800033-JLR200

29. Chwetzoff S, Tsunasawa S, Sakiyama F, Ménez A. Nigexine, a Phospholipase A2 from cobra venom with cytotoxic properties not related to esterase activity. J Biol Chem. 1989 Aug;264(22):13289- 97. https://doi.org/10.1016/S0021-9258(18)51627-6

30. Roberto PG, Kashima S, Marcussi S, Pereira JO, Astolfi-Filho S, Nomizo A, et al. Cloning and identification of a complete cDNA coding for a bactericidal and antitumoral acidic phospholipase A 2 from Bothrops jararacussu Venom. Protein J. 2004;23(4):273-85. https://doi.org/10.1023/B:JOPC.0000027852.92208.60

31. Kennedy AR. Chemopreventive agents: protease inhibitors. Epidemiol Data Suggest. Pharmacol. Ther. 1998;78:167-209. https://doi.org/10.1016/S0163-7258(98)00010-2

32. Young A, Byung MI, Lee MU, Yeong ', Kim S. Characterization and cytotoxicity of L-amino acid oxidase from the venom of king cobra (Ophiopkagus hannah). Int J Biochem Cell Biol. 1997;29:911-9. https://doi.org/10.1016/S1357-2725(97)00024-1

33. Zhang L, Wu WT. Isolation and characterization of ACTX-6: A cytotoxic L-amino acid oxidase from Agkistrodon acutus snake venom. Nat Prod Res. 2008 Apr 15;22(6):554-63. https://doi.org/10.1080/14786410701592679

34. Zhang L, Wei LJ. ACTX-8, a cytotoxic l-amino acid oxidase isolated from Agkistrodon acutus snake venom, induces apoptosis in Hela cervical cancer cells. Life Sci. 2007 Mar 6;80(13):1189-97. https://doi.org/10.1016/j.lfs.2006.12.024

35. Lm G, Sanchez EF, Sg S, Santos RG. Tumor cytotoxicity of Leucurolysin-B, a P-III snake venom metalloproteinase from Bothrops leucurus. J Venomous Anim Toxins Include Trop Dis. 2012;18(1):24-33. https://doi.org/10.1590/S1678-91992012000100004

36. Ârio M, Âsar C, Ãa C, Maria DA, Moura-Da-Silva AM, Pizzocaro KF, et al. Inhibition of melanoma cells tumorigenicity by the snake venom toxin jararhagin. Available from: www.elsevier.com/locate/ toxicon

37. Higuchi DA, Almeida MC, Barros CC, Sanchez EF, Pesquero PR, Lang EAS, et al. Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth. Toxicon. 2011 Jul;58(1):123-9. https://doi.org/10.1016/j.toxicon.2011.05.013

38. Swaim MW, Chiang2 HS, Huang2 TF. Characterisation of platelet aggregation induced by PC-3 human prostate adenocarcinoma cells and inhibited by venom peptides, trigramin and rhodostomin. Eur J Cancer. 1996 Apr;32A(4):715-21. https://doi.org/10.1016/0959-8049(95)00648-6

39. Chung KH, Kim SH, Han K yeon, Sohn YD, Chang SI, Baek KH, et al. Inhibitory effect of salmosin, a Korean snake venomderived disintegrin, on the integrin αv-mediated proliferation of SK-Mel-2 human melanoma cells. J Pharm Pharmacol. 2010 Feb 18;55(11):1577-82. https://doi.org/10.1211/0022357022160

40. Soszka T, Knudsen KA, Lucia Beviglia J, Rossi C, Poggi A, Niewiarowski S, et al. Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, an RGD-containing peptide isolated from the venom of Trimeresurus albolabris. Exp Cell Res. 1991 Sep;196(1):6-12. https://doi.org/10.1016/0014-4827(91)90449-5

41. Google Books. Handbook of Venoms and Toxins of Reptiles. [cited 2023 Jan 5]. Available from: https://books.google.co.in/ books?hl=en&lr=&id=x_vME799de4C&oi=fnd&pg=PA173&d-q=Doley+R,+Zhou+X,+Kini+RM.+Snake+venom+phospho-lipase+A2+enzymes.+In:+Handbook+of+venoms+and+tox-ins+of+reptiles.+CRC+Press/Taylor+and+Francis+Group%3B+20 09.+p.+173%E2%80%93205.&ots=PzK50HB-Qg&sig=lrutuXB¬ZH9Sll2tOfgFwD-i6as0&redir_esc=y#v=onepage&q&f=false

42. Dennis EA, Cao J, Hsu YH, Magrioti V, Kokotos G. Phospholipase A2 enzymes: Physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem Rev. 2011 Oct 12;111(10):6130-85. https://doi.org/10.1021/cr200085w

43. Gutiérrez J, Lomonte B. Phospholipase A2 myotoxins from Bothrops snake venoms. Toxicon. 1995 Nov 1;33(11):1405-24. https://doi.org/10.1016/0041-0101(95)00085-Z

44. Kini RM. Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon. 2003 Dec 1;42(8):827-40. https://doi.org/10.1016/j.toxicon.2003.11.002

45. Berg OG, Gelb MH, Tsai MD, Jain MK. Interfacial enzymology: the secreted phospholipase A2-paradigm. Chem Rev. 2001 Sep;101(9):2613-53. https://doi.org/10.1021/cr990139w

46. Rowan EG. What does β-bungarotoxin do at the neuromuscular junction? Toxicon. 2001 Jan 1;39(1):107-18. https://doi.org/10.1016/S0041-0101(00)00159-8

47. Doley R, Kini RM. Protein complexes in snake venom. Cell Mol Life Sci. 2009 Jun 4;66(17):2851-71. https://doi.org/10.1007/s00018-009-0050-2

48. Kwong PD, McDonald NQ, Sigler PB, Hendrickson WA. Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action. Structure. 1995;3(10):1109-19. https://doi.org/10.1016/S0969-2126(01)00246-5

49. Rodrigues R, Izidoro LF, de Oliveira Jr. R, Soares A, Rodrigues V, Sampaio S. Snake venom phospholipases A2: a new class of antitumor agents. Protein Pept Lett. 2009 Aug 1;16(8):894-8. https://doi.org/10.2174/092986609788923266

50. Benati RB, Costa TR, Cacemiro MDC, Sampaio SV, De Castro FA, Burin SM. Cytotoxic and pro-apoptotic action of MjTX-I, a phospholipase A2 isolated from Bothrops moojeni snake venom, towards leukemic cells. J Venom Anim Toxins Incl Trop Dis. 2018 Dec 20;24(1):40. https://doi.org/10.1186/s40409-018-0180-9

51. Marcussi S, Santos PRS, Menaldo DL, Silveira LB, Santos-Filho NA, Mazzi M V., et al. Evaluation of the genotoxicity of Crotalus durissus terrificus snake venom and its isolated toxins on human lymphocytes. Mutat Res Genet Toxicol Environ Mutagen. 2011 Sep 18;724(1-2):59-63. https://doi.org/10.1016/j.mrgentox.2011.06.004

52. Lomonte B, Angulo Y, Calderón L. An overview of lysine-49 phospholipase A2 myotoxins from crotalid snake venoms and their structural determinants of myotoxic action. Toxicon. 2003;42:885-901. https://doi.org/10.1016/j.toxicon.2003.11.008

53. Fujisawa D, Yamazaki Y, Lomonte B, Morita T. Catalytically inactive phospholipase A2 homologue binds to vascular endothelial growth factor receptor-2 via a C-terminal loop region. Biochem J. 2008 May 1;411(3):515-22. https://doi.org/10.1042/BJ20080078

54. Kessentini-Zouari R, Jebali J, Taboubi S, Srairi-Abid N, Morjen M, Kallech-Ziri O, et al. CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo. Lab Investig. 2010;90:510-9. https://doi.org/10.1038/labinvest.2009.137

55. Bazaa A, Limam I, Kessentini-Zouari R, Kallech-Ziri O, El Battari A, Braguer D, et al. MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions. Available from: www. plosone.org

56. Bazaa A, Luis J, Srairi-Abid N, Kallech-Ziri O, Kessentini-Zouari R, Defilles C, et al. MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration. Matrix Biol. 2009 May 1;28(4):188-93. https://doi.org/10.1016/j.matbio.2009.03.007

57. Corin RE, Viskatis LJ, Vidal JC, Etcheverry MA. Cytotoxicity of crotoxin on murine erythroleukemia cells in vitro. Investig New Drugs. 1993;11(1):11-15 https://doi.org/10.1007/BF00873905

58. Muller SP, Silva VAO, Silvestrini AVP, de Macedo LH, Caetano GF, Reis RM, et al. Crotoxin from Crotalus durissus terrificus venom: in vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines. Toxicon. 2018;156:13-22. https://doi.org/10.1016/j.toxicon.2018.10.306

59. Bezerra PHA, Ferreira IM, Franceschi BT, Bianchini F, Ambrósio L, Cintra ACO, et al. BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation. J Venom Anim Toxins Incl Trop Dis. 2019 Jul 29;25:e20190010. https://doi.org/10.1590/1678-9199-jvatitd-2019-0010

60. Khunsap S, Pakmanee N, Khow O, Chanhome L, Sitprija V, Suntravat M, et al. Purification of a phospholipase A 2 from Daboia russelii siamensis venom with anticancer effects. J Venom Res. 2011;2:42-51.

61. Jain D, Kumar S. Snake venom: a potent anticancer agent. Asian Pac J Cancer Prev. 2012 ;13(10):4855-60. https://doi.org/10.7314/APJCP.2012.13.10.4855

62. Fox JW, Serrano SMT. Timeline of key events in snake venom metalloproteinase research. J Proteomics. 2009 Mar 6;72(2):200-9. https://doi.org/10.1016/j.jprot.2009.01.015

63. Ferreira BA, Deconte SR, de Moura FBR, Tomiosso TC, Clissa PB, Andrade SP, et al. Inflammation, angiogenesis and fibrogenesis are differentially modulated by distinct domains of the snake venom metalloproteinase jararhagin. Int J Biol Macromol. 2018 ;119:1179- 87. https://doi.org/10.1016/j.ijbiomac.2018.08.051

64. Markland FS, Swenson S. Snake venom metalloproteinases. Toxicon. 2013 Feb ;62:3-18. https://doi.org/10.1016/j.toxicon.2012.09.004

65. Gutiérrez JM, Escalante T, Rucavado A, Herrera C. Hemorrhage caused by snake venom metalloproteinases: a journey of discovery and understanding. Toxins. 2016;8(4):93. https://doi.org/10.3390/toxins8040093

66. Sanchez EF, Flores-Ortiz RJ, Alvarenga VG, Eble JA. Direct fibrinolytic snake venom metalloproteinases affecting hemostasis: structural, biochemical features and therapeutic potential. Toxins. 2017 ;9(12):392. https://doi.org/10.3390/toxins9120392

67. Kini RM, Koh CY. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites. Toxins. 2016;8(10):284. https://doi.org/10.3390/toxins8100284

68. Woodside DG, Vanderslice P. Inflammation and regulation by integrin cell adhesion antagonists. Transl Inflam. 2019 Jan 1;2019:43-68. https://doi.org/10.1016/B978-0-12-813832-8.00003-0

69. Olaoba OT, Karina dos Santos P, Selistre-de-Araujo HS, Ferreira de Souza DH. Snake venom metalloproteinases (SVMPs): a structure-function update. Toxicon X. 2020 Sep 1;7:100052. https://doi.org/10.1016/j.toxcx.2020.100052

70. Onyango OK. Isolation and characterization of snake venom proteins and peptides from members of Viperidae and Elapidae snake families from Kilifi County. 2018 [cited 2022 Aug 16]. Available from: http:// localhost/xmlui/handle/123456789/4764

71. Calderon LA, Sobrinho JC, Zaqueo KD, De Moura AA, Grabner AN, Mazzi M V, et al. Antitumoral activity of snake venom proteins: new trends in cancer therapy. 2014 [cited 2023 Sep 16]. Available from: http://dx.doi.org/10.1155/2014/203639 https://doi.org/10.1155/2014/203639

72. Maria AA, da Silva LGL, Correia CC, Ruiz GRG. Antiproliferative effect of the Jararhagin toxin on B16F10 murine melanoma. BMC Complement Altern Med. 2014 Nov 18;14(1):446. https://doi.org/10.1186/1472-6882-14-446

73. Ma R, Mahadevappa R, Kwok HF. Venom-based peptide therapy: insights into anti-cancer mechanism. Oncotarget. 2017; 2017:8. https://doi.org/10.18632/oncotarget.21740

74. Leonardi A, Sajevic T, Kova?i? L, Punger?ar J, Lang Balija M, Halassy B, et al. Hemorrhagin VaH4, a covalent heterodimeric P-III metalloproteinase from Vipera ammodytes ammodytes with a potential antitumour activity. Toxicon. 2014 Jan 1;77:141-55. https://doi.org/10.1016/j.toxicon.2013.11.009

75. Guimarães D de O, Lopes DS, Azevedo FVPV, Gimenes SNC, Silva MA, Achê DC, et al. In vitro antitumor and antiangiogenic effects of Bothropoidin, a metalloproteinase from Bothrops pauloensis snake venom. Int J Biol Macromol. 2017 Apr 1;97:770-7. https://doi.org/10.1016/j.ijbiomac.2017.01.064

76. Escalante T, Rucavado A, Fox JW, Gutiérrez JM. Key events in microvascular damage induced by snake venom hemorrhagic metalloproteinases. J Proteomics. 2011 ;74(9):1781-94. https://doi.org/10.1016/j.jprot.2011.03.026

77. Gutiérrez JM, Rucavado A, Escalante T, Díaz C. Hemorrhage induced by snake venom metalloproteinases: biochemical and biophysical mechanisms involved in microvessel damage. Toxicon. 2005 ;45(8):997-1011. https://doi.org/10.1016/j.toxicon.2005.02.029

78. Akhtar B, Muhammad F, Sharif A, Anwar MI. Mechanistic insights of snake venom disintegrins in cancer treatment. Eur J Pharmacol. 2021;899:174022. https://doi.org/10.1016/j.ejphar.2021.174022

79. Galán JA, Sánchez EE, Rodríguez-Acosta A, Soto JG, Bashir S, McLane MA, et al. Inhibition of lung tumor colonization and cell migration with the disintegrin crotatroxin 2 isolated from the venom of Crotalus atrox. Toxicon. 2008 Jun 1;51(7):1186-96. https://doi.org/10.1016/j.toxicon.2008.02.004

80. McLane MA, Joerger T, Mahmoud A. Disintegrins in health and disease. Front Biosci. 2008 May 1;13(17):6617-37 https://doi.org/10.2741/3177

81. Calvete JJ. The continuing saga of snake venom disintegrins. Toxicon. 2013 Feb 1;62:40-9. https://doi.org/10.1016/j.toxicon.2012.09.005

82. Hammouda MB, Montenegro MF, Sánchez-Del-Campo L, Zakraoui O, Aloui Z, Riahi-Chebbi I, et al. Lebein, A snake venom disintegrin, Induces apoptosis in human melanoma cells. Toxins (Basel). 2016 Jul 5;8:7. https://doi.org/10.3390/toxins8070206

83. Hong SY, Lee H, You WK, Chung KH, Kim DS, Song K. The snake venom disintegrin salmosin induces apoptosis by disassembly of focal adhesions in bovine capillary endothelial cells. Biochem Biophys Res Commun. 2003 Mar 14;302(3):502-8. https://doi.org/10.1016/S0006-291X(03)00213-4

84. Ghazaryan N, Movsisyan N, Macedo JC, Vaz S, Ayvazyan N, Pardo L, et al. The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model. Invest New Drugs. 2019 Oct 1;37(5):1044-51. https://doi.org/10.1007/s10637-019-00734-2

85. Lino RLB, dos Santos PK, Pisani GFD, Altei WF, Cominetti MR, Selistre-de-Araújo HS. Alphavbeta3 integrin blocking inhibits apoptosis and induces autophagy in murine breast tumor cells. Biochim Biophys Acta. 2019 Dec 1;1866(12):118536. https://doi.org/10.1016/j.bbamcr.2019.118536

86. Danilucci TM, Santos PK, Pachane BC, Pisani GFD, Lino RLB, Casali BC, et al. Recombinant RGD-disintegrin DisBa-01 blocks integrin α v β 3 and impairs VEGF signaling in endothelial cells. Cell Commun Signal. 2019 Mar 20;17(1):27. https://doi.org/10.1186/s12964-019-0339-1

87. Chan YS, Cheung RCF, Xia L, Wong JH, Ng TB, Chan WY. Snake venom toxins: toxicity and medicinal applications. Appl Microbiol Biotechnol. . 2016 ;100(14):6165-81. https://doi.org/10.1007/s00253-016-7610-9

88. Costal-Oliveira F, Stransky S, Guerra-Duarte C, Naves de Souza DL, Vivas-Ruiz DE, Yarlequé A, et al. L-amino acid oxidase from Bothrops atrox snake venom triggers autophagy, apoptosis and necrosis in normal human keratinocytes. Sci Rep. 2019 ;9(1):781. https://doi.org/10.1038/s41598-018-37435-4

89. Ullah A, Masood R, Spencer PJ, Murakami MT, Arni RK. Crystallization and preliminary X-ray diffraction studies of an L-amino-acid oxidase from Lachesis muta venom. Acta Crystallogr F Struct Biol Commun. 2014 ;70(Pt 11):1556-9. https://doi.org/10.1107/S2053230X14017877

90. Kazianis S, Della Coletta L, Morizot DC, Johnston DA, Osterndorff EA, Nairn RS. Overexpression of a fish CDKN2 gene in a hereditary melanoma model. Carcinogenesis. 2000 ;21(4):599-605. https://doi.org/10.1093/carcin/21.4.599

91. Hanukoglu I. Proteopedia: Rossmann fold: a beta-alpha-beta fold at dinucleotide binding sites. Biochem Mol Biol Educ. 2015 May 1;43(3):206-9. https://doi.org/10.1002/bmb.20849

92. Pawelek PD, Cheah J, Coulombe R, Macheroux P, Ghisla S, Vrielink A. The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site. EMBO J. 2000 Aug 15;19(16):4204-15. https://doi.org/10.1093/emboj/19.16.4204

93. Ullah A. Structure-function studies and mechanism of action of snake venom L-amino acid oxidases. Front Pharmacol. 2020 Feb 25;11:110. https://doi.org/10.3389/fphar.2020.00110

94. Lazo F, Vivas-Ruiz DE, Sandoval GA, Rodríguez EF, Kozlova EEG, Costal-Oliveira F, et al. Biochemical, biological and molecular characterization of an L-Amino acid oxidase (LAAO) purified from Bothrops pictus Peruvian snake venom. Toxicon. 2017 ;139:74-86. https://doi.org/10.1016/j.toxicon.2017.10.001

95. Takatsuka H, Sakurai Y, Yoshioka A, Kokubo T, Usami Y, Suzuki M, et al. Molecular characterization of l-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet aggregation. Biochim Biophys Acta. 2001 Jan 12;1544(1-2):267-77. https://doi.org/10.1016/S0167-4838(00)00229-6

96. Izidoro LFM, Ribeiro MC, Souza GRL, Sant'Ana CD, Hamaguchi A, Homsi-Brandeburgo MI, et al. Biochemical and functional characterization of an l-amino acid oxidase isolated from Bothrops pirajai snake venom. Bioorg Med Chem. 2006 Oct 15;14(20):7034- 43. https://doi.org/10.1016/j.bmc.2006.06.025

97. Toyama MH, Toyama DDO, Passero LFD, Laurenti MD, Corbett CE, Tomokane TY, et al. Isolation of a new L-amino acid oxidase from Crotalus durissus cascavella venom. Toxicon. 2006 Jan ;47(1):47- 57. https://doi.org/10.1016/j.toxicon.2005.09.008

98. Rey-Suárez P, Acosta C, Torres U, Saldarriaga-Córdoba M, Lomonte B, Núñez V. MipLAAO, a new L-amino acid oxidase from the redtail coral snake Micrurus mipartitus. PeerJ. 2018 ;2018(6):e4924. https://doi.org/10.7717/peerj.4924

99. Tempone AG, Spencer PJ, Lourenço CO, Rogero JR, Nascimento N, Andrade HF. Bothrops moojeni venom kills Leishmania spp. with hydrogen peroxide generated by its L-amino acid oxidase. Biochem Biophys Res Commun. 2001 ;280(3):620-4. https://doi.org/10.1006/bbrc.2000.4175

100. Costa TR, Menaldo DL, Zoccal KF, Burin SM, Aissa AF, Castro FAD, et al. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer. Sci Rep. 2017 ;7(1):1- 12. https://doi.org/10.1038/srep42673

101. Sant'Ana CD, Menaldo DL, Costa TR, Godoy H, Muller VDM, Aquino VH, et al. RETRACTED: Antiviral and antiparasite properties of an l-amino acid oxidase from the Snake Bothrops jararaca: Cloning and identification of a complete cDNA sequence. Biochem Pharmacol. 2008 Jul 15;76(2):279-88. https://doi.org/10.1016/j.bcp.2008.05.003

102. NUUTINEN JT, Timonen S. Identification of nitrogen mineralization enzymes, l-amino acid oxidases, from the ectomycorrhizal fungi Hebeloma spp. and Laccaria bicolor. Mycol Res. 2008 Dec 1;112(12):1453-64. https://doi.org/10.1016/j.mycres.2008.06.023

103. Arima J, Sasaki C, Sakaguchi C, Mizuno H, Tamura T, Kashima A, et al. Structural characterization of l-glutamate oxidase from Streptomyces sp. X-119-6. FEBS J. 2009 ;276(14):3894-903. https://doi.org/10.1111/j.1742-4658.2009.07103.x

104. Schriek S, Kahmann U, Staiger D, Pistorius EK, Michel KP. Detection of an L-amino acid dehydrogenase activity in Synechocystis sp. PCC 6803. J Exp Bot. 2009 Mar ;60(3):1035. https://doi.org/10.1093/jxb/ern352

105. Nishizawa T, Aldrich CC, Sherman DH. Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243. J Bacteriol. 2005 Mar ;187(6):2084- 92. https://doi.org/10.1128/JB.187.6.2084-2092.2005

106. Matés JM, Sánchez-Jiménez FM. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol. 2000 Feb 1;32(2):157-70. https://doi.org/10.1016/S1357-2725(99)00088-6

107. Singh M, Sharma H, Singh N. Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. Mitochondrion. 2007 Dec;7(6):367-73. https://doi.org/10.1016/j.mito.2007.07.003

108. Burin SM, Ayres LR, Neves RP, Ambrósio L, De Morais FR, Dias- Baruffi M, et al. L-amino acid oxidase isolated from bothrops pirajai induces apoptosis in BCR-ABL-positive cells and potentiates imatinib mesylate effect. Basic Clin Pharmacol Toxicol. 2013 Aug;113(2):103-12. https://doi.org/10.1111/bcpt.12073

109. Alves RM, Antonucci GA, Paiva HH, Cintra ACO, Franco JJ, Mendonça-Franqueiro EP, et al. Evidence of caspase-mediated apoptosis induced by l-amino acid oxidase isolated from Bothrops atrox snake venom. Comp Biochem Physiol. 2008;151(4):542-50. https://doi.org/10.1016/j.cbpa.2008.07.007

110. Abdelkafi-Koubaa Z, Elbini-Dhouib I, Souid S, Jebali J, Doghri R, Srairi-Abid N, et al. Pharmacological investigation of CC-LAAO, an L-Amino acid oxidase from Cerastes cerastes snake venom. Toxins. 2021 ;13(12):904. https://doi.org/10.3390/toxins13120904

111. Zhang L, Cui L. A cytotoxin isolated from Agkistrodon acutus snake venom induces apoptosis via Fas pathway in A549 cells. Toxicol in Vitro. 2007 Sep 1;21(6):1095-103. https://doi.org/10.1016/j.tiv.2007.04.008

112. Teixeira TL, Oliveira Silva VA, da Cunha DB, Polettini FL, Thomaz CD, Pianca AA, et al. Isolation, characterization and screening of the in vitro cytotoxic activity of a novel L-amino acid oxidase (LAAOcdt) from Crotalus durissus terrificus venom on human cancer cell lines. Toxicon. 2016 Sep 1;119:203-17. https://doi.org/10.1016/j.toxicon.2016.06.009

113. Momic T, Cohen G, Reich R, Arlinghaus FT, Eble JA, Marcinkiewicz C, et al. Vixapatin (VP12), a C-type lectin-protein from Vipera xantina palestinae venom: Characterization as a novel anti-angiogenic compound. Toxins (Basel). 2012 Oct;4(10):862-77. https://doi.org/10.3390/toxins4100862

114. De Castro Damasio D, Nolte S, Polak LP, Brandt AP, Bonan NB, Zischler L, et al. The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line. Toxicon. 2014;90:299-307. https://doi.org/10.1016/j.toxicon.2014.08.062

115. Pathan J, Mondal S, Sarkar A, Chakrabarty D. Daboialectin, a C-type lectin from Russell's viper venom induces cytoskeletal damage and apoptosis in human lung cancer cells in vitro. Toxicon. 2017 Mar 1;127:11-21. https://doi.org/10.1016/j.toxicon.2016.12.013

116. Bonilla-Porras AR, Vargas LJ, Jimenez-Del-Rio M, Nuñez V, Velez- Pardo C. Purification of nasulysin-1: A new toxin from Porthidium nasutum snake venom that specifically induces apoptosis in leukemia cell model through caspase-3 and apoptosis-inducing factor activation. Toxicon. 2016 Sep 15;120:166-74. https://doi.org/10.1016/j.toxicon.2016.08.006

117. Boldrini-França J, Pinheiro-Junior EL, Peigneur S, Pucca MB, Cerni FA, Borges RJ, et al. Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. Sci Rep. 2020 Dec 1;10(1):4476. https://doi.org/10.1038/s41598-020-61258-x

118. Bittenbinder MA, van Thiel J, Cardoso FC, Casewell NR, Gutiérrez JM, Kool J, et al. Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies. Commun Biol. 2024;7(1):358. https://doi.org/10.1038/s42003-024-06019-6

119. Zhao Y sheng, Yang H ling, Liu C zheng. [Inhibitory effects of immunotargeting of Chinese cobra cytotoxin and iodine-131 against nasopharyngeal carcinoma cells in vitro]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jul 1;28(7):1235-6.

120. Awwad S, Angkawinitwong U. Overview of antibody drug delivery. Pharmaceutics. 2018 Sep 1;10(3):83. https://doi.org/10.3390/pharmaceutics10030083

121. Chenthamara D, Subramaniam S, Ramakrishnan G, Krishnaswamy S, Essa MM, Lin FH, et al. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res. 2019;23:20. https://doi.org/10.1186/s40824-019-0166-x

122. Suralkar AR, Khedkar CS, Zanwar NR, Chandak CC, Gandhi SJ. Liposomes as a novel drug delivery system. GSC Biol Pharm Sci. 2022 Sep 30;20(3):336-43. https://doi.org/10.30574/gscbps.2022.20.3.0372

123. Vatankhah M, Dadashzadeh S, Mahboubi A, Haeri A, Jandaghi Alaee K, Mostafavi Naeini SB, et al. Preparation of multivesicular liposomes for the loco-regional delivery of Vancomycin hydrochloride using active loading method: drug release and antimicrobial properties. J Liposome Res. 2023; https://doi.org/10.1080/08982104.2023.2220805

124. Law LH, Huang J, Xiao P, Liu Y, Chen Z, Lai JHC, et al. Multiple CEST contrast imaging of nose-to-brain drug delivery using iohexol liposomes at 3T MRI. J Control Release. 2023 Feb 1;354:208-20. https://doi.org/10.1016/j.jconrel.2023.01.011

125. Nel J, Elkhoury K, Velot É, Bianchi A, Acherar S, Francius G, et al. Functionalized liposomes for targeted breast cancer drug delivery. Bioactive Mater. 2023;24:401-37. https://doi.org/10.1016/j.bioactmat.2022.12.027

126. Namakshenas P, Mojra A. Efficient drug delivery to hypoxic tumors using thermosensitive liposomes with encapsulated anti-cancer drug under high intensity pulsed ultrasound. Int J Mech Sci. 2023 Jan 1;237:107818. https://doi.org/10.1016/j.ijmecsci.2022.107818

127. Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, Andaloussi S EL, et al. Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev. 2020 Jan 1;159:332- 43. https://doi.org/10.1016/j.addr.2020.04.004

128. Almeida H, Silva AC. Nanoparticles in ocular drug delivery systems. Pharmaceutics. 2023;15:1675. https://doi.org/10.3390/pharmaceutics15061675

129. Baldrick P. Nonclinical testing evaluation of liposomes as drug delivery systems. Int J Toxicol. 2023 Mar-Apr;42(2):122-34. https://doi.org/10.1177/10915818221148436

130. Chen CC, Liu L, Ma F, Wong CW, Guo XE, Chacko JV, et al. Elucidation of exosome migration across the blood-brain barrier model in vitro. Cell Mol Bioeng. 2016 Dec 1;9(4):509-29. https://doi.org/10.1007/s12195-016-0458-3

131. Jimidi Bhaskar S. A Recent advances in drug delivery to brain-a review. Asian J Pharm Res. 2024;14(1):668-87. https://doi.org/10.52711/2231-5691.2024.00013

132. Vader P, Mol EA, Pasterkamp G, Schiffelers RM. Extracellular vesicles for drug delivery . Adv Drug Deliv Rev. 2016;106:148-156. https://doi.org/10.1016/j.addr.2016.02.006

133. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341-5. https://doi.org/10.1038/nbt.1807

134. Reddy SK, Ballal AR, Shailaja S, Seetharam RN, Raghu CH, Sankhe R, et al. Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy. Theranostics. 2023;13(7):2241-55. https://doi.org/10.7150/thno.78426

135. Siddhardha B, Dyavaiah M, Kasinathan K. Model organisms to study biological activities and toxicity of nanoparticles. Springer Singapore; 2020. 1-466 p. https://doi.org/10.1007/978-981-15-1702-0

136. Jimenez-Canale J, Fernández-Quiroz D, Teran-Saavedra NG, Diaz-Galvez KR, Gallegos-Tabanico A, Burgara-Estrella AJ, et al. Cytotoxic activity of Crotalus molossus molossus snake venom-loaded in chitosan nanoparticles against T-47D breast carcinoma cells. Acta Biochim Pol. 2022;69(1):233-43.

137. Çelen Ç, Keçeciler C, Kar?? M, Göçmen B, Yesil-Celiktas O, Nalbantsoy A. Cytotoxicity of silica nanoparticles with transcaucasian nose-horned viper, Vipera ammodytes transcaucasiana, Venom on U87MG and SHSY5Y Neuronal Cancer Cells. Appl Biochem Biotechnol. 2018 Oct 1;186(2):350-7. https://doi.org/10.1007/s12010-018-2742-2

138. Badr G, Al-Sadoon MK, Rabah DM, Sayed D. Snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells. Apoptosis. 2013 Mar;18(3):300-14. https://doi.org/10.1007/s10495-012-0787-1

139. Chen D, Liu X, Lu X, Tian J. Nanoparticle drug delivery systems for synergistic delivery of tumor therapy. Frontiers Media S.A.; 2023. https://doi.org/10.3389/fphar.2023.1111991

140. Srinivas T, Parvathi D, Devi UA. Advancements in nanoparticle applications for targeted drug delivery: benefits and implications. Int J Biol Res. 2024 Jul 26;11(2):50-6. https://doi.org/10.14419/gqvh1v53

141. Ani AC, Emencheta SC, Orah KJ, Upaganlawar AB, Prajapati BG, Oranu CK, et al. Targeted nanotechnology-based formulations. Alzheimer's disease and advanced drug delivery strategies. Elsevier; 2023. p. 347-59. https://doi.org/10.1016/B978-0-443-13205-6.00007-8

142. Whitford W, Guterstam P. Exosome manufacturing status. Future Med Chem. 2019 ;11(10):1225-36. https://doi.org/10.4155/fmc-2018-0417

143. Kishore BK, Park F, Ecelbarger CM, Lv LL, Liu BC, Tang TT, et al. Extracellular vesicles: opportunities and challenges for the treatment of renal diseases. Front Physiol. 2019 ;1:226.

144. Lee JC, Ray RM, Scott TA. Prospects and challenges of tissue-derived extracellular vesicles. Molecular Therapy. Cell Press; 2024. https://doi.org/10.1016/j.ymthe.2024.06.025

145. Lee J, Kim J, Jeong M, Lee H, Goh U, Kim H, et al. Liposome-based engineering of cells to package hydrophobic compounds in membrane vesicles for tumor penetration. Nano Lett. 2015;15(5):2938-44. https://doi.org/10.1021/nl5047494

146. Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014 ;35(7):2383-90. https://doi.org/10.1016/j.biomaterials.2013.11.083

147. Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016 ;12(3):655-64 https://doi.org/10.1016/j.nano.2015.10.012

148. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release. 2015 ;207:18-30. https://doi.org/10.1016/j.jconrel.2015.03.033

149. Li Z, Zhou X, Wei M, Gao X, Zhao L, Shi R, et al. In vitro and in vivo RNA Inhibition by CD9-HuR Functionalized Exosomes Encapsulated with miRNA or CRISPR/dCas9. Nano Lett. 2019 ;19(1):19-28. https://doi.org/10.1021/acs.nanolett.8b02689

150. Feng T, Huang X, Ni R, Suen WLL, Chau Y. Nanoparticles for drug delivery targeting neurodegeneration in brain and eye. Nanomater Drug Deliv Ther. 2019; 2019:149-83. https://doi.org/10.1016/B978-0-12-816505-8.00006-0

151. Yang P, Ren J, Yang L. Nanoparticles in the new era of cardiovascular therapeutics: challenges and opportunities. Int J Mol Sci. 2023; 2023:24. https://doi.org/10.3390/ijms24065205

152. Alkufi H, Salman A, Taher S. Principles and Advantages of New Drug Delivery Technologie. J Complem Med Res. 2023;14(3):6. https://doi.org/10.5455/jcmr.2023.14.03.02

153. Hami Z. A Brief review on advantages of nano-based drug delivery systems. Ann Milit Health Sci Res. 2021 Mar 6;19(1):541-69. https://doi.org/10.5812/amh.112274

154. Wang L, Song Y, Wang H, Zhang X, Wang M, He J, et al. Advances of artificial intelligence in anti-cancer drug design: a review of the past decade. Pharmaceuticals. 2023;16:253. https://doi.org/10.3390/ph16020253

155. Tan P, Chen X, Zhang H, Wei Q, Luo K. Artificial intelligence aids in development of nanomedicines for cancer management. Semin Cancer Biol. 2023 Feb 1;89:61-75. https://doi.org/10.1016/j.semcancer.2023.01.005

156. Moebius K, Eichler J. HIV-derived peptide mimics. Drug Discov Today Technol. 2009 Jan 1;6(1-4):e19-25. https://doi.org/10.1016/j.ddtec.2009.09.001

157. Díaz-Gómez JL, Martín-Estal I, Rivera-Aboytes E, Gaxiola-Muñíz RA, Puente-Garza CA, García-Lara S, et al. Biomedical applications of synthetic peptides derived from venom of animal origin: a systematic review. Biomed Pharmacother. 2024;170:116015. https://doi.org/10.1016/j.biopha.2023.116015

Article Metrics
34 Views 21 Downloads 55 Total

Year

Month

Related Search

By author names