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Investigation of the Cytotoxicity of Fig, Lemon, Olive, and Turnip Exosomes on MCF-7 Cells

Year 2019, Cilt 22 (Ek Sayı 2), 382 - 387, 31.12.2019
https://doi.org/10.18016/ksutarimdoga.v22i49454.589845

Abstract

With their nano-sized structure, exosomes are involved
in a wide variety of cellular processes such as genetic information flow,
immune system modulations, intercellular communication, and pathophysiological
changes. The use of exosomes are exponentially growing particularly in the
areas of identification of biomarkers, development of nanocarriers for
effective drug delivery, and vaccine production. In recent years, edible plant
derived exosomes gained much interest with their strong antimicrobial
activities, modulatory activities on the intestinal stem cells, and the
anticancer activities. In this study, the cytotoxic effects of fig, lemon, olive and turnip derived
exosomes were investigated through the neutral red uptake assay. It was
observed that 100 µg/mL protein containing lemon and turnip derived exosomes
inhibited the cell proliferation significantly, on the other hand, fig and
olive derived exosomes did not alter the proliferation of MCF-7 cells. Since
the results for the cytotoxic activity of turnip exosomes are original in this
research, it was found worthy to emphasis the utility of turnip exosomes for
the development of new anticancer agents or new drug delivery nanocarriers.

References

  • An Q, Huckelhoven R, Kogel K-H, van Bel AJE 2006. Multivesicular bodies participate in a cell wall-associated defence response in barley leaves attacked by the pathogenic powdery mildew fungus. Cellular Microbiology, 8(6): 1009–1019.
  • Böhlenius H, Mørch SM, Godfrey D, Nielsen ME, Thordal-Christensen H 2010. The Multivesicular Body-Localized GTPase ARFA1b/1c Is Important for Callose Deposition and ROR2 Syntaxin-Dependent Preinvasive Basal Defense in Barley. The Plant Cell, 22(11): 3831–3844.
  • Boriachek K, Islam MN, Möller A, Salomon C, Nguyen N-T, Hossain MSA, Yamauchi Y, Shiddiky MJA 2018. Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles. Small, 14(6): 1702153. https://doi.org/ 10.1002/smll.201702153
  • Deatherage BL, Cookson BT 2012. Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life. Infection and Immunity, 80(6): 1948–1957.
  • Deng Z, Rong Y, Teng Y, Mu J, Zhuang X, Tseng M, Samykutty A, Zhang L, Yan J, Miller D, Suttles J, Zhang H-G 2017. Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase. Molecular Therapy, 25(7): 1641–1654.
  • Dragomir M, Chen B, Calin GA 2018. Exosomal lncRNAs as new players in cell-to-cell communication. Translational Cancer Research, 7(S2): S243–S252. https://doi.org/10.21037/ tcr.2017.10.46
  • Escudier B, Dorval T, Chaput N, André F, Caby M-P, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq J-B, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L 2005. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. Journal of Translational Medicine, 3(1): 10.
  • Farag MA, Motaal AAA 2010. Sulforaphane composition, cytotoxic and antioxidant activity of crucifer vegetables. Journal of Advanced Research, 1(1): 65–70.
  • Hoshino A, Costa-Silva B, Shen T-L, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Jørgen Labori K, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D 2015. Tumour exosome integrins determine organotropic metastasis. Nature, 527(7578): 329–335. https://doi.org/10.1038/nature15756
  • Karaosmanoğlu O, Banerjee S, Sivas H 2018. Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells. Cellular Oncology, 41(4): 439–453. https://doi.org/10.1007/s13402-018-0384-6
  • Kibria G, Ramos EK, Wan Y, Gius DR, Liu H 2018. Exosomes as a Drug Delivery System in Cancer Therapy: Potential and Challenges. Molecular Pharmaceutics, 15(9): 3625–3633.
  • Li X-B, Zhang Z-R, Schluesener HJ, Xu S-Q 2006. Role of exosomes in immune regulation. Journal of Cellular and Molecular Medicine, 10(2): 364–375. https://doi.org/10.1111/j.1582-4934.2006.tb00405.x
  • Ma Q-L, Teng E, Zuo X, Jones M, Teter B, Zhao EY, Zhu C, Bilousova T, Gylys KH, Apostolova LG, LaDu MJ, Hossain MA, Frautschy SA, Cole GM 2018. Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer’s disease. Neurobiology of Disease, 114: 120–128. https://doi.org/10.1016/j.nbd.2018.02.014
  • Meyer D, Pajonk S, Micali C, O’Connell R, Schulze-Lefert P 2009. Extracellular transport and integration of plant secretory proteins into pathogen-induced cell wall compartments. The Plant Journal, 57(6): 986–999.
  • Min H, Sun X, Yang X, Zhu H, Liu J, Wang Y, Chen G, Sun X 2018. Exosomes Derived from Irradiated Esophageal Carcinoma-Infiltrating T Cells Promote Metastasis by Inducing the Epithelial–Mesenchymal Transition in Esophageal Cancer Cells. Pathology & Oncology Research, 24(1): 11–18. https://doi.org/10.1007/s12253-016-0185-z
  • Mincheva-Nilsson L, Baranov V 2010. The Role of Placental Exosomes in Reproduction. American Journal of Reproductive Immunology, 63(6): 520–533.
  • Mineo M, Garfield SH, Taverna S, Flugy A, De Leo G, Alessandro R, Kohn EC 2012. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion. Angiogenesis, 15(1): 33–45.
  • Mu J, Zhuang X, Wang Q, Jiang H, Deng Z, Wang B, Zhang L, Kakar S, Jun Y, Miller D, Zhang H 2014. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome‐like nanoparticles. Molecular Nutrition & Food Research, 58(7): 1561–1573.
  • Nagarajah S 2016. Exosome Secretion - More Than Simple Waste Disposal? Implications for Physiology, Diagnostics and Therapeutics. Journal of circulating biomarkers, 5: 7. https://doi.org/ 10.5772/62975
  • Pant S, Hilton H, Burczynski ME 2012. The multifaceted exosome: Biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochemical Pharmacology, 83(11): 1484–1494.
  • Raimondo S, Naselli F, Fontana S, Monteleone F, Lo Dico A, Saieva L, Zito G, Flugy A, Manno M, Di Bella MA, De Leo G, Alessandro R 2015. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 6(23): 19514–27. https://doi.org/ 10.18632/oncotarget.4004
  • Schorey JS, Bhatnagar S 2008. Exosome Function: From Tumor Immunology to Pathogen Biology. Traffic, 9(6): 871–881.
  • Théry C, Amigorena S, Raposo G, Clayton A 2006. Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. Current Protocols in Cell Biology, 30(1): 3.22.1-3.22.29. https://doi.org/10.1002/0471143030.cb0322s30
  • Van Niel G, D’Angelo G, Raposo G 2018. Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19(4): 213–228. https://doi.org/10.1038/nrm.2017.125
  • Wang B, Zhuang X, Deng Z-B, Jiang H, Mu J, Wang Q, Xiang X, Guo H, Zhang L, Dryden G, Yan J, Miller D, Zhang H-G 2014. Targeted Drug Delivery to Intestinal Macrophages by Bioactive Nanovesicles Released from Grapefruit. Molecular Therapy, 22(3): 522–534. https://doi.org/10.1038/mt.2013.190
  • Wang L, Wang J, Fang L, Zheng Z, Zhi D, Wang S, Li S, Ho C-T, Zhao H 2014. Anticancer activities of citrus peel polymethoxyflavones related to angiogenesis and others. Biomed Research International, 2014: 453972. https://doi.org/ 10.1155/2014/453972
  • Wang Q, Ren Y, Mu J, Egilmez NK, Zhuang X, Deng Z, Zhang L, Yan J, Miller D, Zhang H-G 2015. Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites. Cancer Research, 75(12): 2520–2529.
  • Xiao J, Feng S, Wang X, Long K, Luo Y, Wang Y, Ma J, Tang Q, Jin L, Li X, Li M 2018. Identification of exosome-like nanoparticle-derived microRNAs from 11 edible fruits and vegetables. PeerJ, 6: e5186. https://doi.org/10.7717/peerj.5186
  • Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M 2013. Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Promote Functional Recovery and Neurovascular Plasticity After Stroke in Rats. J. Cereb. Journal of Cerebral Blood Flow & Metababolism, 33(11): 1711–1715.
  • Zhuang X, Deng Z-B, Mu J, Zhang L, Yan J, Miller D, Feng W, McClain CJ, Zhang H-G 2015. Ginger-derived nanoparticles protect against alcohol-induced liver damage. Journal of Extracellular Vesicles, 4(1): 28713. https://doi.org/10.3402/ jev.v4.28713

İncir, Limon, Zeytin ve Turp Ekzozomlarının MCF-7 Hücrelerinde Sitotoksik Etkisinin Araştırılması

Year 2019, Cilt 22 (Ek Sayı 2), 382 - 387, 31.12.2019
https://doi.org/10.18016/ksutarimdoga.v22i49454.589845

Abstract

Nano-boyutlu yapılarıyla ekzozomlar genetik bilgi
akışı, immun sistem düzenlenmesi ve patofizyolojik değişiklikler gibi çok
çeşitli hücresel süreçlere dahil olurlar. Ekzozomların, özellikle biyoişaret
tanımlanması, etkin ilaç dağıtımı için nanotaşıyıcıların geliştirilmesi ve aşı
üretilmesi alanlarında kullanımları hızla artmaktadır. Son yıllarda yenilebilir
bitkilerden türevlenen ekzozomlar yüksek antimikrobiyal etkileri, bağırsak kök
hücreleri üzerinde düzenleyici etkileri ve antikanser etkileriyle ilgi
çekmektedir.
Bu çalışmada incir, limon, zetin ve turp türevli ekzozomların sitotoksik etkileri
nötral kırmızısı alım testiyle araştırılmıştır. Protein miktarı 100 µg/mL olan
limon ve turp ekzozomlarının hücre çoğalmasını engellediği gözlenirken incir ve
zeytin türevli ekzozomların MCF-7 çoğalmasını etkilemediği görülmüştür. Turp
ekzozomlarının sitotoksistik aktivitesi sonuçları, bu araştırmada orijinal
olduğu için, yeni antikanser ajanlarının veya yeni ilaç dağıtım
nanotaşıyıcılarının geliştirilmesi için turp ekzozomları kullanımına vurgu
yapmanın değerli olabileceği düşünülmüştür.

References

  • An Q, Huckelhoven R, Kogel K-H, van Bel AJE 2006. Multivesicular bodies participate in a cell wall-associated defence response in barley leaves attacked by the pathogenic powdery mildew fungus. Cellular Microbiology, 8(6): 1009–1019.
  • Böhlenius H, Mørch SM, Godfrey D, Nielsen ME, Thordal-Christensen H 2010. The Multivesicular Body-Localized GTPase ARFA1b/1c Is Important for Callose Deposition and ROR2 Syntaxin-Dependent Preinvasive Basal Defense in Barley. The Plant Cell, 22(11): 3831–3844.
  • Boriachek K, Islam MN, Möller A, Salomon C, Nguyen N-T, Hossain MSA, Yamauchi Y, Shiddiky MJA 2018. Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles. Small, 14(6): 1702153. https://doi.org/ 10.1002/smll.201702153
  • Deatherage BL, Cookson BT 2012. Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life. Infection and Immunity, 80(6): 1948–1957.
  • Deng Z, Rong Y, Teng Y, Mu J, Zhuang X, Tseng M, Samykutty A, Zhang L, Yan J, Miller D, Suttles J, Zhang H-G 2017. Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase. Molecular Therapy, 25(7): 1641–1654.
  • Dragomir M, Chen B, Calin GA 2018. Exosomal lncRNAs as new players in cell-to-cell communication. Translational Cancer Research, 7(S2): S243–S252. https://doi.org/10.21037/ tcr.2017.10.46
  • Escudier B, Dorval T, Chaput N, André F, Caby M-P, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq J-B, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L 2005. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. Journal of Translational Medicine, 3(1): 10.
  • Farag MA, Motaal AAA 2010. Sulforaphane composition, cytotoxic and antioxidant activity of crucifer vegetables. Journal of Advanced Research, 1(1): 65–70.
  • Hoshino A, Costa-Silva B, Shen T-L, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Jørgen Labori K, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D 2015. Tumour exosome integrins determine organotropic metastasis. Nature, 527(7578): 329–335. https://doi.org/10.1038/nature15756
  • Karaosmanoğlu O, Banerjee S, Sivas H 2018. Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells. Cellular Oncology, 41(4): 439–453. https://doi.org/10.1007/s13402-018-0384-6
  • Kibria G, Ramos EK, Wan Y, Gius DR, Liu H 2018. Exosomes as a Drug Delivery System in Cancer Therapy: Potential and Challenges. Molecular Pharmaceutics, 15(9): 3625–3633.
  • Li X-B, Zhang Z-R, Schluesener HJ, Xu S-Q 2006. Role of exosomes in immune regulation. Journal of Cellular and Molecular Medicine, 10(2): 364–375. https://doi.org/10.1111/j.1582-4934.2006.tb00405.x
  • Ma Q-L, Teng E, Zuo X, Jones M, Teter B, Zhao EY, Zhu C, Bilousova T, Gylys KH, Apostolova LG, LaDu MJ, Hossain MA, Frautschy SA, Cole GM 2018. Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer’s disease. Neurobiology of Disease, 114: 120–128. https://doi.org/10.1016/j.nbd.2018.02.014
  • Meyer D, Pajonk S, Micali C, O’Connell R, Schulze-Lefert P 2009. Extracellular transport and integration of plant secretory proteins into pathogen-induced cell wall compartments. The Plant Journal, 57(6): 986–999.
  • Min H, Sun X, Yang X, Zhu H, Liu J, Wang Y, Chen G, Sun X 2018. Exosomes Derived from Irradiated Esophageal Carcinoma-Infiltrating T Cells Promote Metastasis by Inducing the Epithelial–Mesenchymal Transition in Esophageal Cancer Cells. Pathology & Oncology Research, 24(1): 11–18. https://doi.org/10.1007/s12253-016-0185-z
  • Mincheva-Nilsson L, Baranov V 2010. The Role of Placental Exosomes in Reproduction. American Journal of Reproductive Immunology, 63(6): 520–533.
  • Mineo M, Garfield SH, Taverna S, Flugy A, De Leo G, Alessandro R, Kohn EC 2012. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion. Angiogenesis, 15(1): 33–45.
  • Mu J, Zhuang X, Wang Q, Jiang H, Deng Z, Wang B, Zhang L, Kakar S, Jun Y, Miller D, Zhang H 2014. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome‐like nanoparticles. Molecular Nutrition & Food Research, 58(7): 1561–1573.
  • Nagarajah S 2016. Exosome Secretion - More Than Simple Waste Disposal? Implications for Physiology, Diagnostics and Therapeutics. Journal of circulating biomarkers, 5: 7. https://doi.org/ 10.5772/62975
  • Pant S, Hilton H, Burczynski ME 2012. The multifaceted exosome: Biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochemical Pharmacology, 83(11): 1484–1494.
  • Raimondo S, Naselli F, Fontana S, Monteleone F, Lo Dico A, Saieva L, Zito G, Flugy A, Manno M, Di Bella MA, De Leo G, Alessandro R 2015. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 6(23): 19514–27. https://doi.org/ 10.18632/oncotarget.4004
  • Schorey JS, Bhatnagar S 2008. Exosome Function: From Tumor Immunology to Pathogen Biology. Traffic, 9(6): 871–881.
  • Théry C, Amigorena S, Raposo G, Clayton A 2006. Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. Current Protocols in Cell Biology, 30(1): 3.22.1-3.22.29. https://doi.org/10.1002/0471143030.cb0322s30
  • Van Niel G, D’Angelo G, Raposo G 2018. Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19(4): 213–228. https://doi.org/10.1038/nrm.2017.125
  • Wang B, Zhuang X, Deng Z-B, Jiang H, Mu J, Wang Q, Xiang X, Guo H, Zhang L, Dryden G, Yan J, Miller D, Zhang H-G 2014. Targeted Drug Delivery to Intestinal Macrophages by Bioactive Nanovesicles Released from Grapefruit. Molecular Therapy, 22(3): 522–534. https://doi.org/10.1038/mt.2013.190
  • Wang L, Wang J, Fang L, Zheng Z, Zhi D, Wang S, Li S, Ho C-T, Zhao H 2014. Anticancer activities of citrus peel polymethoxyflavones related to angiogenesis and others. Biomed Research International, 2014: 453972. https://doi.org/ 10.1155/2014/453972
  • Wang Q, Ren Y, Mu J, Egilmez NK, Zhuang X, Deng Z, Zhang L, Yan J, Miller D, Zhang H-G 2015. Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites. Cancer Research, 75(12): 2520–2529.
  • Xiao J, Feng S, Wang X, Long K, Luo Y, Wang Y, Ma J, Tang Q, Jin L, Li X, Li M 2018. Identification of exosome-like nanoparticle-derived microRNAs from 11 edible fruits and vegetables. PeerJ, 6: e5186. https://doi.org/10.7717/peerj.5186
  • Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M 2013. Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Promote Functional Recovery and Neurovascular Plasticity After Stroke in Rats. J. Cereb. Journal of Cerebral Blood Flow & Metababolism, 33(11): 1711–1715.
  • Zhuang X, Deng Z-B, Mu J, Zhang L, Yan J, Miller D, Feng W, McClain CJ, Zhang H-G 2015. Ginger-derived nanoparticles protect against alcohol-induced liver damage. Journal of Extracellular Vesicles, 4(1): 28713. https://doi.org/10.3402/ jev.v4.28713
There are 30 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section RESEARCH ARTICLE
Authors

Oğuzhan Karaosmanoğlu 0000-0003-2028-7339

Publication Date December 31, 2019
Submission Date July 10, 2019
Acceptance Date August 23, 2019
Published in Issue Year 2019Cilt 22 (Ek Sayı 2)

Cite

APA Karaosmanoğlu, O. (2019). Investigation of the Cytotoxicity of Fig, Lemon, Olive, and Turnip Exosomes on MCF-7 Cells. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 22, 382-387. https://doi.org/10.18016/ksutarimdoga.v22i49454.589845


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