Assessment of the Anti-cancer Effects of Camel Milk Exosomes (CMEXOs) on Murine Colorectal Cancer Cell Line (CT-26)
-
Samira Karbasi
,
Nafiseh Erfanian
,
Hamideh Dehghan
,
Asghar Zarban
,
mahammad hasan Namaei
,
Mohammad Yahya Hanafi-Bojd
,
Saeed nasseri
Abstract
Today, camel milk consumption in the Middle East is trendy because it is believed that it reduces the risk of cancer. Recently, studies have discovered that most of milk's beneficial effects are because of its nanoparticles, especially exosomes. The objective of the present research was to investigate the anti-cancer effects of camel milk exosomes (CMEXOs) in the murine colorectal cancer cell line (CT-26).
Our findings verified the existence of exosomes measuring approximately 114.1±3.4 nm in diameter. Through MTT and migration assays, we established that CMEXOs exhibit dose-dependent anti-proliferative and anti-migration effects on the CT-26 cell line. Furthermore, our study showed that treatment with CMEXOs led to a reduction in TNF-α and IL-6 gene expression in CT-26 cells.
While additional in vivo studies are required, our data demonstrate that CMEXOs have anti-proliferative and anti-migration effects on CT-26, possibly by influencing crucial genes within the inflammation pathway.
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12. Bunggulawa EJ, Wang W, Yin T, Wang N, Durkan C, Wang Y, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnology. 2018;16(1):1-13.
13. Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36:301-12.
14. Reif S, Elbaum Shiff Y, Golan-Gerstl R. Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner. J Transl Med. 2019;17:1-10.
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17. Javeed N, Mukhopadhyay D. Exosomes and their role in the micro-/macro-environment: a comprehensive review. J Biomed Res. 2017;31(5):386.
18. Zempleni J, Aguilar-Lozano A, Sadri M, Sukreet S, Manca S, Wu D, et al. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J Nutr. 2017;147(1):3-10.
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20. Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 2016;371(1):48-61.
21. Pieters BC, Arntz OJ, Bennink MB, Broeren MG, van Caam AP, Koenders MI, et al. Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β. PLoS One. 2015;10(3):e0121123.
22. Nam GH, Choi Y, Kim GB, Kim S, Kim SA, Kim IS. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy. J Adv Mater. 2020;32(51):2002440.
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24. Wadhonkar K, Singh N, Heralde III FM, Parihar SP, Hirani N, Baig MS. Exosome-derived miRNAs regulate macrophage-colorectal cancer cell cross-talk during aggressive tumor development. Colorectal Cancer. 2023;12(1):CRC40.
25. Han J-H, Park D, Jung B, Yoo H-G, Cho K-O, Kim E. Exosomal delivery of Fas-associated factor 1 (FAF1), a multifunctional tumor suppressor and genuine exosome cargo, effectively antagonizes tumor growth. Cancer Res. 2023;83(7_Supplement):1728-.
26. Elsayed R, Elashiry M, Tran C, Yang T, Carroll A, Liu Y, et al. Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune Modulation. Int J Mol Sci. 2023;24(14):11306.
27. Kheradjoo H, Nouralishahi A, Hoseinzade Firozabdi MS, Mohammadzadehsaliani S. Mesenchymal stem/stromal (MSCs)-derived exosome inhibits retinoblastoma Y-79 cell line proliferation and induces their apoptosis. Nanomed Res J. 2022;7(3):264-9.
28. Wang L, Xu P, Xie X, Hu F, Jiang L, Hu R, et al. Down regulation of SIRT2 reduced ASS induced NSCLC apoptosis through the release of autophagy components via exosomes. Front cell dev biol. 2020;8:601953.
29. Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC, et al. Rab27a supports exosome-dependent and-independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012;72(19):4920-30.
30. Wang Z, Chen J-Q, Liu J-L, Tian L. Exosomes in tumor microenvironment: novel transporters and biomarkers. J Transl Med. 2016;14(1):1-9.
31. Chen Q, Zu M, Gong H, Ma Y, Sun J, Ran S, et al. Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation. J Nanobiotechnology. 2023;21(1):1-19.
32. Rezaei R, Baghaei K, Hashemi SM, Zali MR, Ghanbarian H, Amani D. Tumor-derived exosomes enriched by miRNA-124 promote anti-tumor immune response in CT-26 tumor-bearing mice. Frontiers in med. 2021;8:619939.
33. Asadirad A, Baghaei K, Hashemi SM, Dehnavi S, Ghanbarian H, Mortaz E, et al. Dendritic cell immunotherapy with miR-155 enriched tumor-derived exosome suppressed cancer growth and induced antitumor immune responses in murine model of colorectal cancer induced by CT26 cell line. Int Immunopharmacol. 2022;104:108493.
34. Belluco C, Nitti D, Frantz M, Toppan P, Basso D, Plebani M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol. 2000;7:133-8.
35. El-Kattawy AM, Algezawy O, Alfaifi MY, Noseer EA, Hawsawi YM, Alzahrani OR, et al. Therapeutic potential of camel milk exosomes against HepaRG cells with potent apoptotic, anti-inflammatory, and anti-angiogenesis effects for colostrum exosomes. Biomed Pharmacother. 2021;143:112220.
36. Ali M, Elsayed GR, Salama MF, El-Magd MA. Camel milk exosomes had a selective anticancer effect on PANC1 cells and a proliferative effect on H6c7 cells. KVMJ. 2022;20(1):1-5.
37. Coskun Ö, Oztopuz O, Ozkan O. Determination of IL-6, TNF-alpha and VEGF levels in the serums of patients with colorectal cancer. CMB J. 2017;63(5).
38. Ueda T, Shimada E, Urakawa T. Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol. 1994;29:423-9.
39. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. J Carcinog. 2009;30(7):1073-81.
40. Ibrahim HM, Mohammed-Geba K, Tawfic AA, El-Magd MA. Camel milk exosomes modulate cyclophosphamide-induced oxidative stress and immuno-toxicity in rats. Food Funct. 2019;10(11):7523-32.
2. Wang H, Tian T, Zhang J. Tumor-associated macrophages (TAMs) in colorectal cancer (CRC): from mechanism to therapy and prognosis. Int J Mol Sci. 2021;22(16):8470.
3. Siskova A, Cervena K, Kral J, Hucl T, Vodicka P, Vymetalkova V. Colorectal adenomas—genetics and searching for new molecular screening biomarkers. Int J Mol Sci. 2020;21(9):3260.
4. Cacciola NA, Salzano A, D’Onofrio N, Venneri T, Cicco PD, Vinale F, et al. Buffalo milk whey activates necroptosis and apoptosis in a xenograft model of colorectal cancer. I Int J Mol Sci. 2022;23(15):8464.
5. Althobaiti NA, Raza SHA, BinMowyna MN, Aldawsari RD, Abdelnour SA, Abdel-Hamid M, et al. The potential therapeutic role of camel milk exosomes. Ann Anim Sci. 2022.
6. Khan MZ, Xiao J, Ma Y, Ma J, Liu S, Khan A, et al. Research development on anti-microbial and antioxidant properties of camel milk and its role as an anti-cancer and anti-hepatitis agent. Antioxidants. 2021;10(5):788.
7. Swelum AA, El-Saadony MT, Abdo M, Ombarak RA, Hussein EO, Suliman G, et al. Nutritional, antimicrobial and medicinal properties of Camel’s milk: A review. Saudi J Biol Sci. 2021;28(5):3126-36.
8. Mostafa GA, Bjørklund G, Ayadhi L. Therapeutic effect of camel milk in children with autism: its impact on serum levels of vasoactive intestinal peptide. IJMSCI. 2021;8(10):5698-707.
9. Iigo M, Alexander DB, Long N, Xu J, Fukamachi K, Futakuchi M, et al. Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie. 2009;91(1):86-101.
10. Shariatikia M, Behbahani M, Mohabatkar H. Anticancer activity of cow, sheep, goat, mare, donkey and camel milks and their caseins and whey proteins and in silico comparison of the caseins. Mol Biol Res Commun. 2017;6(2):57.
11. Badawy AA, El-Magd MA, AlSadrah SA. Therapeutic effect of camel milk and its exosomes on MCF7 cells in vitro and in vivo. Integr. Cancer Ther. 2018;17(4):1235-46.
12. Bunggulawa EJ, Wang W, Yin T, Wang N, Durkan C, Wang Y, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnology. 2018;16(1):1-13.
13. Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36:301-12.
14. Reif S, Elbaum Shiff Y, Golan-Gerstl R. Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner. J Transl Med. 2019;17:1-10.
15. Park H-W, Cho SH. Management of Elderly Asthma: Key Questions and Tentative Answers. Allergy Asthma Immunol Res. 2023;15(1):8.
16. Sarko DK, McKinney CE. Exosomes: origins and therapeutic potential for neurodegenerative disease. Front Neurosci. 2017;11:82.
17. Javeed N, Mukhopadhyay D. Exosomes and their role in the micro-/macro-environment: a comprehensive review. J Biomed Res. 2017;31(5):386.
18. Zempleni J, Aguilar-Lozano A, Sadri M, Sukreet S, Manca S, Wu D, et al. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J Nutr. 2017;147(1):3-10.
19. Zhong J, Xia B, Shan S, Zheng A, Zhang S, Chen J, et al. High-quality milk exosomes as oral drug delivery system. Biomater Res. 2021;277:121126.
20. Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 2016;371(1):48-61.
21. Pieters BC, Arntz OJ, Bennink MB, Broeren MG, van Caam AP, Koenders MI, et al. Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β. PLoS One. 2015;10(3):e0121123.
22. Nam GH, Choi Y, Kim GB, Kim S, Kim SA, Kim IS. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy. J Adv Mater. 2020;32(51):2002440.
23. Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F, Ochiya T. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. 2012;287(2):1397-405.
24. Wadhonkar K, Singh N, Heralde III FM, Parihar SP, Hirani N, Baig MS. Exosome-derived miRNAs regulate macrophage-colorectal cancer cell cross-talk during aggressive tumor development. Colorectal Cancer. 2023;12(1):CRC40.
25. Han J-H, Park D, Jung B, Yoo H-G, Cho K-O, Kim E. Exosomal delivery of Fas-associated factor 1 (FAF1), a multifunctional tumor suppressor and genuine exosome cargo, effectively antagonizes tumor growth. Cancer Res. 2023;83(7_Supplement):1728-.
26. Elsayed R, Elashiry M, Tran C, Yang T, Carroll A, Liu Y, et al. Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune Modulation. Int J Mol Sci. 2023;24(14):11306.
27. Kheradjoo H, Nouralishahi A, Hoseinzade Firozabdi MS, Mohammadzadehsaliani S. Mesenchymal stem/stromal (MSCs)-derived exosome inhibits retinoblastoma Y-79 cell line proliferation and induces their apoptosis. Nanomed Res J. 2022;7(3):264-9.
28. Wang L, Xu P, Xie X, Hu F, Jiang L, Hu R, et al. Down regulation of SIRT2 reduced ASS induced NSCLC apoptosis through the release of autophagy components via exosomes. Front cell dev biol. 2020;8:601953.
29. Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC, et al. Rab27a supports exosome-dependent and-independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012;72(19):4920-30.
30. Wang Z, Chen J-Q, Liu J-L, Tian L. Exosomes in tumor microenvironment: novel transporters and biomarkers. J Transl Med. 2016;14(1):1-9.
31. Chen Q, Zu M, Gong H, Ma Y, Sun J, Ran S, et al. Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation. J Nanobiotechnology. 2023;21(1):1-19.
32. Rezaei R, Baghaei K, Hashemi SM, Zali MR, Ghanbarian H, Amani D. Tumor-derived exosomes enriched by miRNA-124 promote anti-tumor immune response in CT-26 tumor-bearing mice. Frontiers in med. 2021;8:619939.
33. Asadirad A, Baghaei K, Hashemi SM, Dehnavi S, Ghanbarian H, Mortaz E, et al. Dendritic cell immunotherapy with miR-155 enriched tumor-derived exosome suppressed cancer growth and induced antitumor immune responses in murine model of colorectal cancer induced by CT26 cell line. Int Immunopharmacol. 2022;104:108493.
34. Belluco C, Nitti D, Frantz M, Toppan P, Basso D, Plebani M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol. 2000;7:133-8.
35. El-Kattawy AM, Algezawy O, Alfaifi MY, Noseer EA, Hawsawi YM, Alzahrani OR, et al. Therapeutic potential of camel milk exosomes against HepaRG cells with potent apoptotic, anti-inflammatory, and anti-angiogenesis effects for colostrum exosomes. Biomed Pharmacother. 2021;143:112220.
36. Ali M, Elsayed GR, Salama MF, El-Magd MA. Camel milk exosomes had a selective anticancer effect on PANC1 cells and a proliferative effect on H6c7 cells. KVMJ. 2022;20(1):1-5.
37. Coskun Ö, Oztopuz O, Ozkan O. Determination of IL-6, TNF-alpha and VEGF levels in the serums of patients with colorectal cancer. CMB J. 2017;63(5).
38. Ueda T, Shimada E, Urakawa T. Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol. 1994;29:423-9.
39. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. J Carcinog. 2009;30(7):1073-81.
40. Ibrahim HM, Mohammed-Geba K, Tawfic AA, El-Magd MA. Camel milk exosomes modulate cyclophosphamide-induced oxidative stress and immuno-toxicity in rats. Food Funct. 2019;10(11):7523-32.
| Files | ||
| Issue | Vol 23 No 3 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i3.15641 | |
| Keywords | ||
| Camel milk Colorectal cancer Exosomes IL-6 TNF-α | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Karbasi S, Erfanian N, Dehghan H, Zarban A, Namaei mahammad hasan, Hanafi-Bojd MY, nasseri S. Assessment of the Anti-cancer Effects of Camel Milk Exosomes (CMEXOs) on Murine Colorectal Cancer Cell Line (CT-26). Iran J Allergy Asthma Immunol. 2024;23(3):321-329.
