Anticancer Activity of Hydatid Cyst Fluid along with Antigen B on Tumors Induced by 4T1 Breast Cancer Cell in a BALB/c Mice Model
,
Abstract
Background: Studies on experimental model of cancer showed that hydatid cyst fluid (HCF) has antitumor activity. We aimed to investigate the effect of HCF and Antigen B (AgB) on 4T1 breast tumor cells in BALB/c mice.
Methods: This study was carried out in the Department of Parasitology, Tarbiat Modares University, Tehran, Iran from 2019 to 2020. There were two control groups of BALB/c mice (one group were injected with aluminum sulfate and another group with PBS), and six groups, injected via the intraperitoneal route with 100, 300 and 500 μg/ml concentrations of HCF, AgB diluted in 100 μl PBS, and alum. Seven days after the last treatment, 7×105 4T1 cells were subcutaneously injected into the right flank of BALB/c mice.
Results: The difference between the mean size of the tumor in the case and control groups was statistically significant (P<0.05). The mean level of cytokines between the case and control groups was statistically significant (P<0.05). Our histopathological studies showed a reduction in both tumor volume and carcinogenesis in groups injected with 300 μg/ml HCF and 500 μg/ml AgB. The antitumor activity of HCF and AgB may be related to the immune responses against these antigens.
Conclusion: We suggest that polarization of the Th1/Th2 ratio toward the Th1 pathway occurred in groups injected with HCF and AgB. More comprehensive and precise experiments using different hydatid cyst components are required to investigate their prophylactic effects on breast cancer.
1. Omidinia N, Zibaei M, Hosseini H, et al. Human hydatidosis in Alborz Province: a 5-year retrospective epidemiological analy-sis of hospitalized cases. Ann Parasitol. 2020;66(4):587–592.
2. Eslahi AV, Olfatifar M, Karim MR, et al. Global incidence of helminthic contamina-tion of vegetables, cucurbits and fruits: A systematic review and meta-analysis. Food Control. 2021;108582.
3. Golassa L, Abebe T, Hailu A. Evaluation of crude hydatid cyst fluid antigens for the serological diagnosis of hydatidosis in cat-tle. J Helminthol. 2011;85(1):100-8.
4. Maleki B, Dalimi A, Majidiani H, et al. Par-asitic Infections of Wild Boars (Sus scrofa) in Iran: A Literature Review. Infect Disord Drug Targets. 2020;20(5):585–597.
5. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108.
6. Love RR, Love SM, Laudico A V. Breast Cancer from a Public Health Perspective. Breast J. 2004;10(2):136-40.
7. Brindley PJ, da Costa JMC, Sripa B. Why does infection with some helminths cause cancer? Trends Cancer. 2015;1(3):174–182.
8. Darani HY, Yousefi M. Parasites and can-cers: Parasite antigens as possible targets for cancer immunotherapy. Future Oncol. 2012;8(12):1529-35.
9. Callejas BE, Martínez-Saucedo D, Terrazas LI. Parasites as negative regulators of can-cer. Biosci Rep. 2018; 38(5): BSR20180935.
10. Tanyeli O, Dereli Y, Mercan I, et al. New World’s old disease: Cardiac hydatid dis-ease and surgical principles. Cardiovasc J Afr. 2017; 1;28(5):304-308.
11. Chookami MB, Sharafi SM, Sefiddashti RR, et al. Effect of two hydatid cyst anti-gens on the growth of melanoma cancer in C57/black mice. J Parasit Dis. 2016;40(4):1170-1173.
12. Zhang W, Ross AG, McManus DP. Mechanisms of Immunity in Hydatid Dis-ease: Implications for Vaccine Develop-ment. J Immunol. 2008;181(10):6679-85.
13. Gao XY, Zhang GH, Huang L. Modula-tion of human melanoma cell proliferation and apoptosis by hydatid cyst fluid of Echinococcus granulosus [Corrigendum]. Onco Targets Ther. 2018;11:1447.
14. Berriel E, Russo S, Monin L, et al. Anti-tumor activity of human hydatid cyst fluid in a murine model of colon cancer. Scien-tific World Journal. 2013;2013:230176.
15. Badri-Chookami M, Sharafi SM, Rafeie R, et al. Effect of alive protoscoleces of hyda-tid cyst on the growth of melanoma cells in mouse model. J Isfahan Med Sch. 2014; 32 (281): 486-492.
16. Siracusano A, Delunardo F, Teggi A, et al. Host-parasite relationship in cystic echino-coccosis: An evolving story. Clin Dev Immunol. 2012; 2012: 639362.
17. Ranasinghe SL, McManus DP. Echinococcus granulosus: cure for cancer revisited. Front Med (Lausanne). 2018;5:60.
18. Rahimi H, Sadjjadi SM, Sarkari B. Perfor-mance of antigen B isolated from different hosts and cyst locations in diagnosis of cystic echinococcosis. Iran J Parasitol. 2011;6(1):12-9.
19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54.
20. Ioppolo S, Notargiacomo S, Profumo E, et al. Immunological responses to antigen B from Echinococcus granulosus cyst fluid in hydatid patients. Parasite Immunol. 1996;18(11):571-8.
21. Badri M, Ghaffarifar F, Hassan ZM, et al. Immunoregulatory effects of somatic ex-tract of Toxocara canis on airway inflamma-tions in murine model. Iran J Parasitol. 2020;15(4):500–510.
22. Maizels R, Yazdanbakhsh M. T-cell regula-tion in helminth parasite infections: impli-cations for inflammatory diseases. Chem Immunol Allergy. 2008;94:112–23.
23. Smallwood TB, Giacomin PR, Loukas A, et al. Helminth immunomodulation in au-toimmune disease. Front Immunol. 2017; 24;8:453.
24. Darani H, Sharafi S, Mokarian F, et al. Therapeutic Effect of Hydatid Cyst Liquid on Melanoma Tumor Growth in Mouse Model. Journal of Advances in Medicine and Medical Research. 2016;18(2):1-7.
25. Yousofi Darani H, Soozangar N, Khorami S, et al. Hydatid cyst protoscolices induce cell death in WEHI-164 fibrosarcoma cells and inhibit the proliferation of baby ham-ster kidney fibroblasts in vitro. J Parasitol Res. 2012; 2012: 304183.
26. Daneshpour S, Kefayat A, Mofid M, et al. Effect of Hydatid Cyst Fluid Antigens on Induction of Apoptosis on Breast Cancer Cells. Adv Biomed Res. 2019; 8: 27.
27. Amirmajdi MM, Sankian M, Mashhadi IE, et al. Apoptosis of human lymphocytes af-ter exposure to hydatid fluid. Iran J Parasi-tol. 2011; 6(2): 9–16.
28. Karadayi S, Arslan S, Sumer Z, et al. Does hydatid disease have protective effects against lung cancer? Mol Biol Rep. 2013;40(8):4701-4
29. Hong C-C, Yao S, McCann SE, et al. Pre-treatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers. Breast Cancer Res Treat. 2013;139(2):477–88.
30. Ni L, Lu J. Interferon gamma in cancer immunotherapy. Cancer Medicine. 2018;7(9):4509-4516.
31. Castro F, Cardoso AP, Gonçalves RM, et al. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Frontiers in Immunology. 2018;9:847.
32. Farsam V, Hassan ZM, Zavaran-Hosseini A, et al. Antitumor and immunomodulato-ry properties of artemether and its ability to reduce CD4 + CD25 + FoxP3 + T reg cells in vivo. Int Immunopharmacol. 2011; 11(11):1802-8.
33. Piccoli L, Meroni V, Genco F, et al. Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver: A stage-specific approach to assess their biological activity. Clin Dev Immunol. 2012; 1;201: 483935.
34. Korkaya H, Liu S, Wicha MS. Breast can-cer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011;121(10):3804–9.
35. Shakibapour M, Shojaie B, Darani HY. Immunization with hydatid cyst wall anti-gens can inhibit breast cancer through changes in serum levels of Th1/Th2 cyto-kines. Int J Prev Med. 2020; 11:189.
36. Daneshpour S, Rostamirad S, Kefayat A, et al. Identifying the most effective hydatid cyst fluid fraction for anticancer vaccina-tion of 4T1 breast tumor-bearing mice. Int J Prev Med. 2019; 10: 143.
37. O’Hara RJ, Greenman J, MacDonald AW, et al. Advanced colorectal cancer is associ-ated with impaired interleukin 12 and en-hanced interleukin 10 production. Clin Cancer Res. 1998; 1;4(8):1943-8.
38. Kanan JHC, Chain BM. Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echi-nococcus granulosus. Immunology. 2006;118(2):271-8.
39. Siracusano A, Riganò R, Ortona E, et al. Immunomodulatory mechanisms during Echinococcus granulosus infection. Exp Parasitol. 2008; 119(4):483-489.
40. Zhang W, Wen H, Li J, et al. Immunology and immunodiagnosis of cystic echino-coccosis: An update. Clin Dev Immunol. 2012; 2012: 101895.
41. Toes REM, Ossendorp F, Offringa R, et al. CD4 T cells and their role in antitumor immune responses. J Exp Med. 1999; 1;189(5):753-6.
42. Siracusano A, Margutti P, Delunardo F, et al. Molecular cross-talk in host-parasite re-lationships: The intriguing immunomodu-latory role of Echinococcus antigen B in cystic echinococcosis. Int J Parasitol. 2008; 1;38(12):1371-6.
43. Dillman RO, Barth NM, Vandermolen LA, et al. Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma? Cancer Biother Ra-diopharm. 2012; 27(6):337-43.
44. Noya V, Bay S, Festari MF, et al. Mucin-like peptides from Echinococcus granulosus in-duce antitumor activity. Int J Oncol. 2013; 43(3):775-84.
45. Zitvogel L, Apetoh L, Ghiringhelli F, et al. The anticancer immune response: Indis-pensable for therapeutic success? J Clin Invest. 2008; 2;118(6):1991-2001.
46. von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, et al. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to pol-ymorphic epithelial mucin. J Clin Oncol. 2000; 18(3):574-83.
47. Daneshpour S, Bahadoran M, Hejazi SH, et al. Common antigens between hydatid cyst and cancers. Adv Biomed Res. 2016; 5: 9.
48. Rad SR, Daneshpour S, Mofid MR, et al. Effect of hydatid cyst antigens on inhibi-tion of melanoma cancer growth in mouse model. Cell Mol Biol (Noisy-le-grand). 2018; 64(12):1-5.
49. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8(3):223–46.
50. Guan W, Zhang X, Wang X, et al. Em-ploying parasite against cancer: A lesson from the canine tapeworm Echinococcus granulocus. Front Pharmacol. 2019; 1137.
2. Eslahi AV, Olfatifar M, Karim MR, et al. Global incidence of helminthic contamina-tion of vegetables, cucurbits and fruits: A systematic review and meta-analysis. Food Control. 2021;108582.
3. Golassa L, Abebe T, Hailu A. Evaluation of crude hydatid cyst fluid antigens for the serological diagnosis of hydatidosis in cat-tle. J Helminthol. 2011;85(1):100-8.
4. Maleki B, Dalimi A, Majidiani H, et al. Par-asitic Infections of Wild Boars (Sus scrofa) in Iran: A Literature Review. Infect Disord Drug Targets. 2020;20(5):585–597.
5. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108.
6. Love RR, Love SM, Laudico A V. Breast Cancer from a Public Health Perspective. Breast J. 2004;10(2):136-40.
7. Brindley PJ, da Costa JMC, Sripa B. Why does infection with some helminths cause cancer? Trends Cancer. 2015;1(3):174–182.
8. Darani HY, Yousefi M. Parasites and can-cers: Parasite antigens as possible targets for cancer immunotherapy. Future Oncol. 2012;8(12):1529-35.
9. Callejas BE, Martínez-Saucedo D, Terrazas LI. Parasites as negative regulators of can-cer. Biosci Rep. 2018; 38(5): BSR20180935.
10. Tanyeli O, Dereli Y, Mercan I, et al. New World’s old disease: Cardiac hydatid dis-ease and surgical principles. Cardiovasc J Afr. 2017; 1;28(5):304-308.
11. Chookami MB, Sharafi SM, Sefiddashti RR, et al. Effect of two hydatid cyst anti-gens on the growth of melanoma cancer in C57/black mice. J Parasit Dis. 2016;40(4):1170-1173.
12. Zhang W, Ross AG, McManus DP. Mechanisms of Immunity in Hydatid Dis-ease: Implications for Vaccine Develop-ment. J Immunol. 2008;181(10):6679-85.
13. Gao XY, Zhang GH, Huang L. Modula-tion of human melanoma cell proliferation and apoptosis by hydatid cyst fluid of Echinococcus granulosus [Corrigendum]. Onco Targets Ther. 2018;11:1447.
14. Berriel E, Russo S, Monin L, et al. Anti-tumor activity of human hydatid cyst fluid in a murine model of colon cancer. Scien-tific World Journal. 2013;2013:230176.
15. Badri-Chookami M, Sharafi SM, Rafeie R, et al. Effect of alive protoscoleces of hyda-tid cyst on the growth of melanoma cells in mouse model. J Isfahan Med Sch. 2014; 32 (281): 486-492.
16. Siracusano A, Delunardo F, Teggi A, et al. Host-parasite relationship in cystic echino-coccosis: An evolving story. Clin Dev Immunol. 2012; 2012: 639362.
17. Ranasinghe SL, McManus DP. Echinococcus granulosus: cure for cancer revisited. Front Med (Lausanne). 2018;5:60.
18. Rahimi H, Sadjjadi SM, Sarkari B. Perfor-mance of antigen B isolated from different hosts and cyst locations in diagnosis of cystic echinococcosis. Iran J Parasitol. 2011;6(1):12-9.
19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54.
20. Ioppolo S, Notargiacomo S, Profumo E, et al. Immunological responses to antigen B from Echinococcus granulosus cyst fluid in hydatid patients. Parasite Immunol. 1996;18(11):571-8.
21. Badri M, Ghaffarifar F, Hassan ZM, et al. Immunoregulatory effects of somatic ex-tract of Toxocara canis on airway inflamma-tions in murine model. Iran J Parasitol. 2020;15(4):500–510.
22. Maizels R, Yazdanbakhsh M. T-cell regula-tion in helminth parasite infections: impli-cations for inflammatory diseases. Chem Immunol Allergy. 2008;94:112–23.
23. Smallwood TB, Giacomin PR, Loukas A, et al. Helminth immunomodulation in au-toimmune disease. Front Immunol. 2017; 24;8:453.
24. Darani H, Sharafi S, Mokarian F, et al. Therapeutic Effect of Hydatid Cyst Liquid on Melanoma Tumor Growth in Mouse Model. Journal of Advances in Medicine and Medical Research. 2016;18(2):1-7.
25. Yousofi Darani H, Soozangar N, Khorami S, et al. Hydatid cyst protoscolices induce cell death in WEHI-164 fibrosarcoma cells and inhibit the proliferation of baby ham-ster kidney fibroblasts in vitro. J Parasitol Res. 2012; 2012: 304183.
26. Daneshpour S, Kefayat A, Mofid M, et al. Effect of Hydatid Cyst Fluid Antigens on Induction of Apoptosis on Breast Cancer Cells. Adv Biomed Res. 2019; 8: 27.
27. Amirmajdi MM, Sankian M, Mashhadi IE, et al. Apoptosis of human lymphocytes af-ter exposure to hydatid fluid. Iran J Parasi-tol. 2011; 6(2): 9–16.
28. Karadayi S, Arslan S, Sumer Z, et al. Does hydatid disease have protective effects against lung cancer? Mol Biol Rep. 2013;40(8):4701-4
29. Hong C-C, Yao S, McCann SE, et al. Pre-treatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers. Breast Cancer Res Treat. 2013;139(2):477–88.
30. Ni L, Lu J. Interferon gamma in cancer immunotherapy. Cancer Medicine. 2018;7(9):4509-4516.
31. Castro F, Cardoso AP, Gonçalves RM, et al. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Frontiers in Immunology. 2018;9:847.
32. Farsam V, Hassan ZM, Zavaran-Hosseini A, et al. Antitumor and immunomodulato-ry properties of artemether and its ability to reduce CD4 + CD25 + FoxP3 + T reg cells in vivo. Int Immunopharmacol. 2011; 11(11):1802-8.
33. Piccoli L, Meroni V, Genco F, et al. Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver: A stage-specific approach to assess their biological activity. Clin Dev Immunol. 2012; 1;201: 483935.
34. Korkaya H, Liu S, Wicha MS. Breast can-cer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011;121(10):3804–9.
35. Shakibapour M, Shojaie B, Darani HY. Immunization with hydatid cyst wall anti-gens can inhibit breast cancer through changes in serum levels of Th1/Th2 cyto-kines. Int J Prev Med. 2020; 11:189.
36. Daneshpour S, Rostamirad S, Kefayat A, et al. Identifying the most effective hydatid cyst fluid fraction for anticancer vaccina-tion of 4T1 breast tumor-bearing mice. Int J Prev Med. 2019; 10: 143.
37. O’Hara RJ, Greenman J, MacDonald AW, et al. Advanced colorectal cancer is associ-ated with impaired interleukin 12 and en-hanced interleukin 10 production. Clin Cancer Res. 1998; 1;4(8):1943-8.
38. Kanan JHC, Chain BM. Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echi-nococcus granulosus. Immunology. 2006;118(2):271-8.
39. Siracusano A, Riganò R, Ortona E, et al. Immunomodulatory mechanisms during Echinococcus granulosus infection. Exp Parasitol. 2008; 119(4):483-489.
40. Zhang W, Wen H, Li J, et al. Immunology and immunodiagnosis of cystic echino-coccosis: An update. Clin Dev Immunol. 2012; 2012: 101895.
41. Toes REM, Ossendorp F, Offringa R, et al. CD4 T cells and their role in antitumor immune responses. J Exp Med. 1999; 1;189(5):753-6.
42. Siracusano A, Margutti P, Delunardo F, et al. Molecular cross-talk in host-parasite re-lationships: The intriguing immunomodu-latory role of Echinococcus antigen B in cystic echinococcosis. Int J Parasitol. 2008; 1;38(12):1371-6.
43. Dillman RO, Barth NM, Vandermolen LA, et al. Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma? Cancer Biother Ra-diopharm. 2012; 27(6):337-43.
44. Noya V, Bay S, Festari MF, et al. Mucin-like peptides from Echinococcus granulosus in-duce antitumor activity. Int J Oncol. 2013; 43(3):775-84.
45. Zitvogel L, Apetoh L, Ghiringhelli F, et al. The anticancer immune response: Indis-pensable for therapeutic success? J Clin Invest. 2008; 2;118(6):1991-2001.
46. von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, et al. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to pol-ymorphic epithelial mucin. J Clin Oncol. 2000; 18(3):574-83.
47. Daneshpour S, Bahadoran M, Hejazi SH, et al. Common antigens between hydatid cyst and cancers. Adv Biomed Res. 2016; 5: 9.
48. Rad SR, Daneshpour S, Mofid MR, et al. Effect of hydatid cyst antigens on inhibi-tion of melanoma cancer growth in mouse model. Cell Mol Biol (Noisy-le-grand). 2018; 64(12):1-5.
49. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8(3):223–46.
50. Guan W, Zhang X, Wang X, et al. Em-ploying parasite against cancer: A lesson from the canine tapeworm Echinococcus granulocus. Front Pharmacol. 2019; 1137.
| Files | ||
| Issue | Vol 17 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v17i2.9542 | |
| Keywords | ||
| Zoonoses Cyst fluid Immunization Breast neoplasms | ||
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How to Cite
1.
Vafae Eslahi A, Ghaffarifar F, Muhammad Hassan Z, Dalimi A. Anticancer Activity of Hydatid Cyst Fluid along with Antigen B on Tumors Induced by 4T1 Breast Cancer Cell in a BALB/c Mice Model. Iran J Parasitol. 2022;17(2):240-249.
