Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability

Özet

Objectives: Cancer cells modulate metabolic pathways to ensure continuity of energy, macromolecules and redoxhomeostasis. Although these vulnerabilities are often targeted individually, targeting all with an enzyme may prove a novel approach. However, therapeutic enzymes are prone to proteolytic degradation and neutralizing antibodies leading to a reduced half-life and effectiveness. We hypothesized that glucose oxidase (GOX) enzyme that catalyzes oxidation of glucose and production of hydrogen peroxide, may hit all these targets by depleting glucose; crippling anabolic pathways and producing reactive oxygen species (ROS); unbalancing redox homeostasis. Methods: We encapsulated GOX in an acrylamide layer and then performed activity assays in denaturizing settings to determine protection provided by encapsulation. Afterwards, we tested the effects of encapsulated (enGOX) and free (fGOX) enzyme on MCF-7 breast cancer cells. Results: GOX preserved 70% of its activity following encapsulation. When fGOX and enGOX treated with guanidinium chloride, fGOX lost approximately 72% of its activity, while enGOX only lost 30%. Both forms demonstrated remarkable resilience against degradation by proteinase K and inhibited viability of MCF-7 cells in an activity-dependent manner. Conclusions: Encapsulation provided protection to GOX against denaturation without reducing its activity, which would prolong half-life of the enzyme when administered intravenously.

Açıklama

Anahtar Kelimeler

Biocompatibility, Cancer Therapy, Glucose Oxidase, MCF-7, Single Enzyme Nanoparticle, Starving-Like Therapy, Therapeutic Enzyme

Kaynak

TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI

WoS Q Değeri

Q4

Scopus Q Değeri

Q4

Cilt

45

Sayı

6

Künye

Rrustemi, T., Geyik, Ö. G., Özkaya, A. B., Öztürk, T. K., Yüce, Z., & Kılınç, A. (2020). Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability. Turkish Journal of Biochemistry, 1(ahead-of-print).