Journals / Türk Biyokimya Dergisi / 2020 / Cilt: 45 - Sayı: 6

Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability

[Akrilamid-enkapsüle glukoz oksidaz meme kanseri hücre canlılığını inhibe etmektedir]

Pages
811–816
Publication Date
2022-11-06
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Both formsdemonstrated remarkable resilience against degradationby proteinase K and inhibited viability of MCF-7 cells in anactivity-dependent manner.Conclusions: Encapsulation provided protection to GOXagainst denaturation without reducing its activity, whichwould prolong half-life of the enzyme when administeredintravenously.

📌 3 Key Takeaways

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Objective & Hypothesis:Objectives: Cancer cells modulate metabolic pathways toensure continuity of energy, macromolecules and redoxhomeostasis.Although these vulnerabilities are often targetedindividually, targeting all with an enzyme may provea novel approach.
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Key Findings & Data:Afterwards,we tested the effects of encapsulated (enGOX) andfree (fGOX) enzyme on MCF-7 breast cancer cells.Results: GOX preserved 70% of its activity followingencapsulation.
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Conclusion & Impact:Both formsdemonstrated remarkable resilience against degradationby proteinase K and inhibited viability of MCF-7 cells in anactivity-dependent manner.Conclusions: Encapsulation provided protection to GOXagainst denaturation without reducing its activity, whichwould prolong half-life of the enzyme when administeredintravenously.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objectives: Cancer cells modulate metabolic pathways toensure continuity of energy, macromolecules and redoxhomeostasis.Although these vulnerabilities are often targetedindividually, targeting all with an enzyme may provea novel approach. However, therapeutic enzymes areprone to proteolytic degradation and neutralizing antibodiesleading to a reduced half-life and effectiveness. Wehypothesized that glucose oxidase (GOX) enzyme thatcatalyzes oxidation of glucose and production of hydrogenperoxide, may hit all these targets by depleting glucose;crippling anabolic pathways and producing reactive oxygenspecies (ROS); unbalancing redox homeostasis.Methods: We encapsulated GOX in an acrylamide layerand then performed activity assays in denaturizing settingsto determine protection provided by encapsulation. Afterwards,we tested the effects of encapsulated (enGOX) andfree (fGOX) enzyme on MCF-7 breast cancer cells.Results: GOX preserved 70% of its activity followingencapsulation. When fGOX and enGOX treated with guanidiniumchloride, fGOX lost approximately 72% of its activity,while enGOX only lost 30%. Both formsdemonstrated remarkable resilience against degradationby proteinase K and inhibited viability of MCF-7 cells in anactivity-dependent manner.Conclusions: Encapsulation provided protection to GOXagainst denaturation without reducing its activity, whichwould prolong half-life of the enzyme when administeredintravenously.

Özet

Giriş: Kanser hücreleri, enerji devamlılığı ilemakromolekül üretimini ve redoks homeostazını sağlamak amacıyla metabolik yolakları modüle ederler. Bu hassas noktalar ilaç geliştirme çalışmalarında ayrı ayrı hedeflense de, tümünü bir enzim aracılığıyla aynı anda hedeflemek yeni bir yaklaşım niteliği taşımaktadır. Bununla birlikte, terapötik enzimler ilaç olarak uygulandığında etkinliğinde azalmaya yol açan proteolitik degradasyon ve nötralize-edici antikorlara açık durumdadır. Amaç: Glukozun oksidasyonunu ve hidrojen peroksit üretimini katalizleyen enzim olan glukoz oksidazın (GOX), mikroçevredeki glukozu tüketerek sentez ve enerji üretim yolaklarını engelleme ve redoks homeostazının dengesini bozacak reaktif oksijen türleri açığa çıkarma yollarıyla tüm bu hedefleri vurabileceği hipotezini kurduk. Materyal ve Metotlar: Enzimi akrilamid tabaka içine enkapsüle ettik ve enkapsülasyon tarafından sağlanan korumanın düzeyini, denatüre edici koşullarda aktivite denemeleri ile belirledik. Son olarak, hem serbest (fGOX) hem de enkapsüle GOX’un (enGOX) MCF-7 meme kanseri hücreleri üzerindeki etkilerini belirledik. Sonuçlar: Enkapsülasyon sonrası GOX, aktivitesinin % 70’ten fazlasını korumuştur. GndCl ile muamele edildiğinde, fGOX aktivitesinin %72’sini kaybederken enGOX aktivitesinin yalnızca %30’unu kaybetmiştir. Her iki form da, proteinaz K ile parçalanmaya karşı kayda değer bir direnç sergilemiş ve MCF-7 meme kanseri hücrelerinin canlılığını aktiviteye bağımlı şekilde inhibe etmiştir. Tartışma: Enkapsülasyon GOX’un aktivitesini azaltmadan denatürasyona karşı koruma sağlamıştır. Bu sayede, intravenöz olarak uygulanması durumunda enzimin yarı ömrü uzatılmıştır.

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Cite This Article

RRUSTEMİ, T., ÖZTÜRK, T. K., YÜCE, Z., KILINÇ, A., ÖZKAYA, A. B., GEYİK, Ö. G. (2022). Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability. Türk Biyokimya Dergisi, Cilt: 45 - Sayı: 6, 811–816. https://ajindex.com/articles/620776

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References (15)

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74
  2. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Canc Feb. 2011;11:85–95
  3. Ben Sahra I, Laurent K, Giuliano S, Larbret F, Ponzio G, Gounon P, et al. Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Canc Res 2010;70:2465–75
  4. Sobin LH, Kidd JG. A metabolic difference between two lines of lymphoma 6C3HED cells in relation to asparagine. Exp Biol Med Jun. 1965;119:325–7
  5. Oettgen HF, Old LJ, Campbell HA, Philips FS, Clarkson BD, Tallal L, et al. Inhibition of leukemias in man by L-asparaginase. Canc Res Dec. 1967;27:2619–31
  6. Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the firstline treatment of children with acute lymphoblastic leukemia (ALL). Oncol Aug. 2007;12:991–8
  7. Narta UK, Kanwar SS, Azmi W. Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia. Crit Rev Oncol Hematol Mar. 2007;61:208–21
  8. Bankar SB, Bule MV, Singhal RS, Ananthanarayan L. Glucose oxidase – an overview. Biotechnol Adv 2009;27:489–501
  9. Yan M, Ge J, Liu Z, Ouyang P. Encapsulation of single enzyme in nanogel with enhanced biocatalytic activity and stability. 2006
  10. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J Feb. 2009;418:29–37
  11. Fan W, Lu N, Huang P, Liu Y, Yang Z, Wang S, et al. Glucoseresponsive sequential generation of hydrogen peroxide and nitric oxide for synergistic cancer starving-like/gas therapy. Angew Chem Int Ed 2017;56:1229–33
  12. He T, Xu H, Zhang Y, Yi S, Cui R, Xing S, et al. Glucose oxidaseinstructed traceable self-oxygenation/hyperthermia dually enhanced cancer starvation therapy. Theranostics 2020;10: 1544–54
  13. Avramis VI, Tiwari PN. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int J Nanomed 2006;1:241–54
  14. Dinda S, Sarkar S, Das PK. Glucose oxidase mediated targeted cancer-starving therapy by biotinylated self-assembled vesicles. Chem Commun Aug. 2018;54:9929–32
  15. Li L, Wang J, Kong H, Zeng Y, Liu G. Functional biomimetic nanoparticles for drug delivery and theranostic applications in cancer treatment. Sci Technol Adv Mat