In Vitro Assessment of the Anti-Proliferative and Anti-Viability Effects of Salivary Gland Extracts from Hyalomma ticks (Acari: Ixodidae) on Human Colorectal Cancer Cells
-
Maryam Tavassoli
,
Mehdi Kadivar
,
Amir Ahmad Akhavan
,
Mohammad Abdigoudarzi
,
Abbas Moridnia
,
Samira Chaibakhsh
,
Mojtaba Beik-mohammadi
,
Mohammad Mehdi Sedaghat
Abstract
Background: The saliva and salivary glands of ticks possess a wide range of immuno-pharmacologically active molecules that effectively modulate the activity of enzymes, antibodies, and amines that have a role in different biological processes. Derived components from saliva and salivary glands of hard ticks Ixodidae have been characterized as potential natural sources for discovering promising anti-cancer drug candidates.
Methods: The anti-cancer activity of salivary gland extracts (SGEs) from Hyalomma anatolicum, Hyalomma dromedarii, Hyalomma marginatum, and Hyalomma schulzei was assessed. MTT assays and flow cytometry were done on the HT-29 colorectal cancer cell line to evaluate the anti-viability and proliferative inhibition.
Results: Based on the MTT assay results, the SGEs from Hy. dromedarii had the highest and lowest substantial anti-viability effects on the HT-29 cancer cell and human foreskin fibroblast (HFF) normal cell, respectively. The cytometric assessment revealed a significant increase in the apoptosis and necrosis ratio of the HT-29 cancer cells after treatment with Hy. dromedarii SGEs.
Conclusion: The results demonstrated that Hy. dromedarii SGEs have significant anti-proliferative, anti-viability, and apoptotic potential. The result of this study suggests that Hy. dromedarii SGEs is an appropriate candidate for further investigations to identify and purify the mechanisms and molecules involved in the anti-cancer activity of the SGEs.
1. Bray F, Laversanne M, Weiderpass E, Soerjomataram I (2021) The ev¬er‐in-creas¬ing importance of cancer as a leading cause of premature death worldwide. Can¬cer. 27(16): 3029–3030.
2. By cause GD (2020) By country and by re-gion. 2000–2019 World Health Organ¬i-zation.
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: Glo¬bocan estimates of incidence and mortal¬ity worldwide for 36 cancers in 185 coun¬tries. CA Cancer J Clin. 71(3): 209–249.
4. Seyed MA (2019) A comprehensive re¬view on Phyllanthus derived natural products as potential chemotherapeutic and im-muno¬modulators for a wide range of hu-man diseases. Biocatal Agric Bio¬tech¬nol. 17: 529–537.
5. Arokiyaraj C, Tamilarasan K, Manikan¬dan R, Janarthanan S (2022) Purification and structural characterization of lectin with antibacterial and anticancer proper¬ties from grubs of hide beetle, Der¬mestes frischii. Int J Biol Macromol. 203: 312–332.
6. Cardoso P, Barton PS, Birkhofer K, Chichor¬ro F, Deacon C, Fartmann T, Fukushima CS, Gaigher R, Habel JC, Hallmann CA (2020) Scientists' warning to humanity on insect extinctions. Biol Conserv. 242: 108426.
7. Dioguardi M, Caloro GA, Laino L, Alo¬visi M, Sovereto D, Crincoli V, Aiuto R, Di-oguardi A, Delillo A, Troiano G (2020) Therapeutic anticancer uses of the active principles of “Rhopalurus junceus” Ven-om. Biomed. 8: 382.
8. Ebenebe C, Okweche S, Okore O, Ok¬poko V, Amobi M, Eze J. N, Ezenyilim¬ba B, Okonkwo M (2021) Arthropods in cos-metics, pharmaceuticals, and medi¬cine. Intech. 96159
9. Hmmati SA, Tabin S (2022) Insect prote¬ase inhibitors; promising inhibitory com-pounds against SARS-CoV-2 main pro-tease. Comput Biol Med. 142: 105228.
10. Lozano-Trujillo LA, Garzon-Perdomo DK, Vargas AC, De los reyes LM, Avi-la-Ro¬driguez MF, Gay OT, Turner LF (2021) Cytotoxic effects of blue scorpi-on ven¬om (Rhopalurus junceus) in a glioblasto¬ma cell line model. Curr Pharm Biotech¬nol. 22(5): 636–645.
11. Saadoun JH, Sogari G, Bernini V, Camorali C, Rossi F, Neviani E, Lazzi C (2022) A critical review of intrinsic and extrinsic antimicrobial properties of in-sects. Trends Food Sci. 122: 40–48.
12. Bartikova P, Kazimirova M, Stibraniova I (2020) Ticks and the effects of their sa-liva on growth factors involved in skin wound healing. J Venom Res. 22 (10): 45–52.
13. Nascimento TG, Vieira PS, Cogo SC, Dias-netipanyj MF, Franca ND, Camara DA, Porcacchia AS, Mendonca RZ, Moreno-amaral AN, Sa PL (2019) Anti-tumoral ef¬fects of Amblyomma sculptum Berlese sa¬liva in neuroblastoma cell lines involve cytoskeletal deconstruction and cell cycle arrest. Rev Bras Parasito Vet. 28(1): 126–133.
14. Sousa AC, Oliveira CJ, Szabo MP, SIL-VA MJ (2018) Anti-neoplastic activity of Amblyomma sculptum, Amblyomma par¬vum, and Rhipicephalus sanguineus tick saliva on breast tumor cell lines. Toxi¬con. 148: 165–171.
15. Azmiera N, Krasilnikova A, Sahudin S, AL-Talib H, Heo C (2022) Antimicrobi-al pep¬tides isolated from insects and their po¬tential applications. J Asia-Pac Entomol. 101892.
16. Meyer-Rochow VB (2017) Therapeutic ar-thropods and other, largely terrestrial, folk-medicinally important inverte¬brates: a com¬parative survey and re¬view. J Eth-nobiol Ethnomed. 13: 1–31.
17. Moretta A, Scieuzo C, Petrone AM, Sal¬via R, Manniello MD, Franco A, Luc¬chetti D, Vassallo A, Vogel H, Sgmbato A (2021) Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields. Front Cell Infect Microbiol. 11: 453– 479.
18. Mylonakis E, Podsialowski L, Mu¬hammed M, Vilcinskas A (2016) Diver¬sity, evo-lution and medical applications of insect antimicrobial peptides. Biol Sci. 371: 20150290.
19. Varunrajan V, Deepa B (2016) Prospect-ing arthropod biomolecules for medici-nal and therapeutic use: Recent break-throughs. Int J Trop Insect Sci. 978–981.
20. Bakshi M, Kim TK, Porter L, Mwangi W, Mulenga A (2019) Amblyomma ameri-canum ticks utilizes countervailing pro and anti-inflammatory proteins to evade host defense. PLOS Pathogens. 15(11): e1008128.
21. Bonnet S, Kazimirova M, Richardson J, Simo L (2018) Tick saliva and its role in pathogen transmission. Skin arthropod vec¬tors. Elsevier. 5: 121–191.
22. Pereira MC, Nodari EF, De Abreu MR, Paiatto LN, Simioni PU, Camargo-Ma-thias MI (2021) Rhipicephalus san-guineus salivary gland extract as a source of im¬munomodulatory mole¬cules. Exp Appl Acarol. 83(3): 387–398.
23. Aounallah H, Fessel MR, Goldfeder MB, Carvalho E, Bensaoud C, Chudzinski-Tavassi AM, Bouattour A, Mghirbi Y, Faria F (2021) rDromaserpin: a novel an-ti-hemostatic serpin, from the salivary glands of the hard tick Hyalomma drom¬edarii. Toxins. 13(12): 913–937.
24. Bensaoud C, Aounallah H, Sciani JM, Far-ia F, Chudzinski-Tavassi AM (2019) Pro¬teomic informed by transcriptomic for sal¬ivary glands components of the camel tick Hyalomma dromedarii. BMC Ge¬nomics. 20(1): 675–687.
25. Braunger K, Ahn J, Jore MM, Johnson S, Tang TT, Pedersen DV, Andersen GR, Lea SM (2022) Structure and function of a family of tick-derived complement inhibitors targeting properdin. Nat Com-mun. 13: 317 –329.
26. Chmelar J, Kotal J, Kovarikova A, Kotsyfakis M (2019) The use of tick sal-ivary proteins as novel therapeutics. Front Physiol. 10: 812–822.
27. Seabrooks L, HU L (2017) Insects: an un-derrepresented resource for the dis¬cov-ery of biologically active natural prod-ucts. Acta Pharm Sin B. 7(4): 409–426.
28. Stibraniova I, Bartikova P, Holikova V, Kazimirova M (2019) Deciphering bio-logical processes at the tick-host inter-face opens new strategies for treatment of human diseases. Front Physiol. 10: 830 –851.
29. Tang J, Fang Y, Han Y, Bai X, Yan X, Zhang Y, Lai R, Zhang Z (2015) YY-39, a tick anti-thrombosis peptide con-taining RGD domain. Peptides. 68: 99–104.
30. Espada C, Cummins H, Gonzales JA, Not-to L, Gaff HD (2021) A comparison of tick collection materials and methods in Southeastern Virginia. J Med Entomol. 58(2): 692–698.
31. Salomon J, Hamer SA, Swei A (2020) A beginner’s guide to collecting questing hard ticks (Acari: Ixodidae): a standard-ized tick dragging protocol. J Insect Sci. 20 (6): 11 –19.
32. Hoogstraal H (1956) African ixodoidea, Department of the Navy, Bureau of Med¬icine and Surgery.
33. Walker AR (2003) Ticks of domestic an-imals in Africa: a guide to identification of species, Bioscience Reports Edin-burgh.
34. Smith PE, Krohn RI, Hermanson GT, Mal¬lia AK, Gartner FH (1985) Meas-urement of protein using bicinchoninic acid. Anal Biochem. 150 (1): 76–85.
35 Mosmann T (1983) Rapid colorimetric as-say for cellular growth and survival: Ap-plication to proliferation and cytotox¬ici-ty assays. J Immunol Methods. 65(1–2): 55–63.
36. Aounallah H, Bensaoud C, Mghirbi Y, Far¬ia F, Chmelar JI, Kotsyfakis M (2020) Tick salivary com¬pounds for targeted im¬munomodulatory therapy. Front Immu¬nol. 11: 583845.
37. Chudzinski-Tavassi AM, Moris KL, Moris, Pacheco MT, Pasqualoto KF (2016) Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates. Biomed Pharmacother. 77: 9–14.
38. Sousa AC, Szabo MP, Oliveira CJ, Silva MJ (2015) Exploring the anti-tumoral ef-fects of tick saliva and derived com-ponents. Toxicon. 102: 69–73.
39. Stappenbeck TS, Miyoshi H (2009) The role of stromal stem cells in tissue re¬gen-eration and wound repair. Science. 324 (5935): 1666–1669.
40. Deslouches B, DI YP (2017) Antimicrobi-al peptides with selective antitumor mech¬anisms: prospect for anticancer ap-plica¬tions. Oncotarget. 8(28): 46635–46651.
41. Ziaja M, Dziedzic A, Szafraniec K (2020) Cecropins in cancer therapies-where we have been? Eur J Pharmacol. 882: 173317.
42. Bensaoud C, Abdelkafi-Koubaa Z, Ben Ma¬brouk H (2017) Hyalomma drome-darii (Acari: Ixodidae) salivary gland ex-tract inhibits angiogenesis and exhibits in vitro antitumor effects. J Med Ento-mol. 54(6): 1476–1482.
43. De Sa Jounior PL, Camara DA, Sciani JM, Porcacchia AS, Fonseca PM, Men¬donca RZ, Elifo-Esposito S, Simons SM (2019) Antiproliferative and antiangio¬genic ef-fect of Amblyomma sculptum (Acari: Ix-odidae) crude saliva in endo¬thelial cells in vitro. Biomed Pharma¬cother. 110: 353–361.
44. Simons MS, De Sa Junior PL, Faria F (2011) The action of Amblyomma cajennense tick saliva in compounds of the he¬mo¬static system and cytotoxicity in tumor cell lines. Biomed Pharma-cother. 65(6): 443–450.
45. Deslouches B, Steckbeck JD, Craigo JK, Doi Y, Burns JL, Montelaro RC (2015) Engineered cationic antimicrobial pep-tides to overcome multidrug resistance by ESKAPE pathogens. Antimicrob Agents Chemother. 59(2): 1329–1333.
46. Destoumieux-Garzon D, Rosa RD, Schmitt P, Barreto C, Vidal-Dupiol J, Mitta G, Gueguen Y, Bachere E (2016) An¬ti¬mi¬crobial peptides in marine inver-tebrate health and disease. Philos Trans R Soc Lond B Biol Sci. 371(1695): 20150300.
2. By cause GD (2020) By country and by re-gion. 2000–2019 World Health Organ¬i-zation.
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: Glo¬bocan estimates of incidence and mortal¬ity worldwide for 36 cancers in 185 coun¬tries. CA Cancer J Clin. 71(3): 209–249.
4. Seyed MA (2019) A comprehensive re¬view on Phyllanthus derived natural products as potential chemotherapeutic and im-muno¬modulators for a wide range of hu-man diseases. Biocatal Agric Bio¬tech¬nol. 17: 529–537.
5. Arokiyaraj C, Tamilarasan K, Manikan¬dan R, Janarthanan S (2022) Purification and structural characterization of lectin with antibacterial and anticancer proper¬ties from grubs of hide beetle, Der¬mestes frischii. Int J Biol Macromol. 203: 312–332.
6. Cardoso P, Barton PS, Birkhofer K, Chichor¬ro F, Deacon C, Fartmann T, Fukushima CS, Gaigher R, Habel JC, Hallmann CA (2020) Scientists' warning to humanity on insect extinctions. Biol Conserv. 242: 108426.
7. Dioguardi M, Caloro GA, Laino L, Alo¬visi M, Sovereto D, Crincoli V, Aiuto R, Di-oguardi A, Delillo A, Troiano G (2020) Therapeutic anticancer uses of the active principles of “Rhopalurus junceus” Ven-om. Biomed. 8: 382.
8. Ebenebe C, Okweche S, Okore O, Ok¬poko V, Amobi M, Eze J. N, Ezenyilim¬ba B, Okonkwo M (2021) Arthropods in cos-metics, pharmaceuticals, and medi¬cine. Intech. 96159
9. Hmmati SA, Tabin S (2022) Insect prote¬ase inhibitors; promising inhibitory com-pounds against SARS-CoV-2 main pro-tease. Comput Biol Med. 142: 105228.
10. Lozano-Trujillo LA, Garzon-Perdomo DK, Vargas AC, De los reyes LM, Avi-la-Ro¬driguez MF, Gay OT, Turner LF (2021) Cytotoxic effects of blue scorpi-on ven¬om (Rhopalurus junceus) in a glioblasto¬ma cell line model. Curr Pharm Biotech¬nol. 22(5): 636–645.
11. Saadoun JH, Sogari G, Bernini V, Camorali C, Rossi F, Neviani E, Lazzi C (2022) A critical review of intrinsic and extrinsic antimicrobial properties of in-sects. Trends Food Sci. 122: 40–48.
12. Bartikova P, Kazimirova M, Stibraniova I (2020) Ticks and the effects of their sa-liva on growth factors involved in skin wound healing. J Venom Res. 22 (10): 45–52.
13. Nascimento TG, Vieira PS, Cogo SC, Dias-netipanyj MF, Franca ND, Camara DA, Porcacchia AS, Mendonca RZ, Moreno-amaral AN, Sa PL (2019) Anti-tumoral ef¬fects of Amblyomma sculptum Berlese sa¬liva in neuroblastoma cell lines involve cytoskeletal deconstruction and cell cycle arrest. Rev Bras Parasito Vet. 28(1): 126–133.
14. Sousa AC, Oliveira CJ, Szabo MP, SIL-VA MJ (2018) Anti-neoplastic activity of Amblyomma sculptum, Amblyomma par¬vum, and Rhipicephalus sanguineus tick saliva on breast tumor cell lines. Toxi¬con. 148: 165–171.
15. Azmiera N, Krasilnikova A, Sahudin S, AL-Talib H, Heo C (2022) Antimicrobi-al pep¬tides isolated from insects and their po¬tential applications. J Asia-Pac Entomol. 101892.
16. Meyer-Rochow VB (2017) Therapeutic ar-thropods and other, largely terrestrial, folk-medicinally important inverte¬brates: a com¬parative survey and re¬view. J Eth-nobiol Ethnomed. 13: 1–31.
17. Moretta A, Scieuzo C, Petrone AM, Sal¬via R, Manniello MD, Franco A, Luc¬chetti D, Vassallo A, Vogel H, Sgmbato A (2021) Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields. Front Cell Infect Microbiol. 11: 453– 479.
18. Mylonakis E, Podsialowski L, Mu¬hammed M, Vilcinskas A (2016) Diver¬sity, evo-lution and medical applications of insect antimicrobial peptides. Biol Sci. 371: 20150290.
19. Varunrajan V, Deepa B (2016) Prospect-ing arthropod biomolecules for medici-nal and therapeutic use: Recent break-throughs. Int J Trop Insect Sci. 978–981.
20. Bakshi M, Kim TK, Porter L, Mwangi W, Mulenga A (2019) Amblyomma ameri-canum ticks utilizes countervailing pro and anti-inflammatory proteins to evade host defense. PLOS Pathogens. 15(11): e1008128.
21. Bonnet S, Kazimirova M, Richardson J, Simo L (2018) Tick saliva and its role in pathogen transmission. Skin arthropod vec¬tors. Elsevier. 5: 121–191.
22. Pereira MC, Nodari EF, De Abreu MR, Paiatto LN, Simioni PU, Camargo-Ma-thias MI (2021) Rhipicephalus san-guineus salivary gland extract as a source of im¬munomodulatory mole¬cules. Exp Appl Acarol. 83(3): 387–398.
23. Aounallah H, Fessel MR, Goldfeder MB, Carvalho E, Bensaoud C, Chudzinski-Tavassi AM, Bouattour A, Mghirbi Y, Faria F (2021) rDromaserpin: a novel an-ti-hemostatic serpin, from the salivary glands of the hard tick Hyalomma drom¬edarii. Toxins. 13(12): 913–937.
24. Bensaoud C, Aounallah H, Sciani JM, Far-ia F, Chudzinski-Tavassi AM (2019) Pro¬teomic informed by transcriptomic for sal¬ivary glands components of the camel tick Hyalomma dromedarii. BMC Ge¬nomics. 20(1): 675–687.
25. Braunger K, Ahn J, Jore MM, Johnson S, Tang TT, Pedersen DV, Andersen GR, Lea SM (2022) Structure and function of a family of tick-derived complement inhibitors targeting properdin. Nat Com-mun. 13: 317 –329.
26. Chmelar J, Kotal J, Kovarikova A, Kotsyfakis M (2019) The use of tick sal-ivary proteins as novel therapeutics. Front Physiol. 10: 812–822.
27. Seabrooks L, HU L (2017) Insects: an un-derrepresented resource for the dis¬cov-ery of biologically active natural prod-ucts. Acta Pharm Sin B. 7(4): 409–426.
28. Stibraniova I, Bartikova P, Holikova V, Kazimirova M (2019) Deciphering bio-logical processes at the tick-host inter-face opens new strategies for treatment of human diseases. Front Physiol. 10: 830 –851.
29. Tang J, Fang Y, Han Y, Bai X, Yan X, Zhang Y, Lai R, Zhang Z (2015) YY-39, a tick anti-thrombosis peptide con-taining RGD domain. Peptides. 68: 99–104.
30. Espada C, Cummins H, Gonzales JA, Not-to L, Gaff HD (2021) A comparison of tick collection materials and methods in Southeastern Virginia. J Med Entomol. 58(2): 692–698.
31. Salomon J, Hamer SA, Swei A (2020) A beginner’s guide to collecting questing hard ticks (Acari: Ixodidae): a standard-ized tick dragging protocol. J Insect Sci. 20 (6): 11 –19.
32. Hoogstraal H (1956) African ixodoidea, Department of the Navy, Bureau of Med¬icine and Surgery.
33. Walker AR (2003) Ticks of domestic an-imals in Africa: a guide to identification of species, Bioscience Reports Edin-burgh.
34. Smith PE, Krohn RI, Hermanson GT, Mal¬lia AK, Gartner FH (1985) Meas-urement of protein using bicinchoninic acid. Anal Biochem. 150 (1): 76–85.
35 Mosmann T (1983) Rapid colorimetric as-say for cellular growth and survival: Ap-plication to proliferation and cytotox¬ici-ty assays. J Immunol Methods. 65(1–2): 55–63.
36. Aounallah H, Bensaoud C, Mghirbi Y, Far¬ia F, Chmelar JI, Kotsyfakis M (2020) Tick salivary com¬pounds for targeted im¬munomodulatory therapy. Front Immu¬nol. 11: 583845.
37. Chudzinski-Tavassi AM, Moris KL, Moris, Pacheco MT, Pasqualoto KF (2016) Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates. Biomed Pharmacother. 77: 9–14.
38. Sousa AC, Szabo MP, Oliveira CJ, Silva MJ (2015) Exploring the anti-tumoral ef-fects of tick saliva and derived com-ponents. Toxicon. 102: 69–73.
39. Stappenbeck TS, Miyoshi H (2009) The role of stromal stem cells in tissue re¬gen-eration and wound repair. Science. 324 (5935): 1666–1669.
40. Deslouches B, DI YP (2017) Antimicrobi-al peptides with selective antitumor mech¬anisms: prospect for anticancer ap-plica¬tions. Oncotarget. 8(28): 46635–46651.
41. Ziaja M, Dziedzic A, Szafraniec K (2020) Cecropins in cancer therapies-where we have been? Eur J Pharmacol. 882: 173317.
42. Bensaoud C, Abdelkafi-Koubaa Z, Ben Ma¬brouk H (2017) Hyalomma drome-darii (Acari: Ixodidae) salivary gland ex-tract inhibits angiogenesis and exhibits in vitro antitumor effects. J Med Ento-mol. 54(6): 1476–1482.
43. De Sa Jounior PL, Camara DA, Sciani JM, Porcacchia AS, Fonseca PM, Men¬donca RZ, Elifo-Esposito S, Simons SM (2019) Antiproliferative and antiangio¬genic ef-fect of Amblyomma sculptum (Acari: Ix-odidae) crude saliva in endo¬thelial cells in vitro. Biomed Pharma¬cother. 110: 353–361.
44. Simons MS, De Sa Junior PL, Faria F (2011) The action of Amblyomma cajennense tick saliva in compounds of the he¬mo¬static system and cytotoxicity in tumor cell lines. Biomed Pharma-cother. 65(6): 443–450.
45. Deslouches B, Steckbeck JD, Craigo JK, Doi Y, Burns JL, Montelaro RC (2015) Engineered cationic antimicrobial pep-tides to overcome multidrug resistance by ESKAPE pathogens. Antimicrob Agents Chemother. 59(2): 1329–1333.
46. Destoumieux-Garzon D, Rosa RD, Schmitt P, Barreto C, Vidal-Dupiol J, Mitta G, Gueguen Y, Bachere E (2016) An¬ti¬mi¬crobial peptides in marine inver-tebrate health and disease. Philos Trans R Soc Lond B Biol Sci. 371(1695): 20150300.
| Files | ||
| Issue | Vol 17 No 4 (2023) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/jad.v17i4.15298 | |
| Keywords | ||
| Tick Hyalomma Salivary gland extrac Anti-cancer HT-29 cell line | ||
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How to Cite
1.
Tavassoli M, Kadivar M, Akhavan AA, Abdigoudarzi M, Moridnia A, Chaibakhsh S, Beik-mohammadi M, Sedaghat MM. In Vitro Assessment of the Anti-Proliferative and Anti-Viability Effects of Salivary Gland Extracts from Hyalomma ticks (Acari: Ixodidae) on Human Colorectal Cancer Cells. J Arthropod Borne Dis. 2024;17(4):352–363.
