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

With their nano-sized structure, exosomes are involved in a widevariety of cellular processes such as genetic information flow, immunesystem modulations, intercellular communication, andpathophysiological changes. The use of exosomes are exponentiallygrowing particularly in the areas of identification of biomarkers,development of nanocarriers for effective drug delivery, and vaccineproduction. In recent years, edible plant derived exosomes gained muchinterest with their strong antimicrobial activities, modulatoryactivities on the intestinal stem cells, and the anticancer activities.In this study, the cytotoxic effects of fig, lemon, olive and turnip derivedexosomes were investigated through the neutral red uptake assay. Itwas observed that 100 µg/mL protein containing lemon and turnipderived exosomes inhibited the cell proliferation significantly, on theother hand, fig and olive derived exosomes did not alter theproliferation of MCF-7 cells. Since the results for the cytotoxic activityof turnip exosomes are original in this research, it was found worthy toemphasis the utility of turnip exosomes for the development of newanticancer agents or new drug delivery nanocarriers.

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

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

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An Q, Huckelhoven R, Kogel K-H, van Bel AJE 2006. Multivesicular bodies participate in a cell wallassociated 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 SyntaxinDependent 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, SchulzeLefert 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. Gingerderived nanoparticles protect against alcoholinduced liver damage. Journal of Extracellular Vesicles, 4(1): 28713. https://doi.org/10.3402/ jev.v4.28713