Fabrication of bimetallic AgZnO nanocomposite and its anti-cancer activity on cervical cancer via impeding PI3K/AKT/mTOR pathway

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INTRODUCTION: Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (AgZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer.

METHODS: The process of generating bimetallic nanoparticles (NPs), namely AgZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated.

RESULTS: Bimetallic AgZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90 nm, and their zeta potential was -14.70 mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24 hours of treatment, a dosage of 5 µg/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins.

CONCLUSIONS: The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic AgZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:84

Enthalten in:

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) - 84(2024) vom: 20. März, Seite 127437

Sprache:

Englisch

Beteiligte Personen:

Yin, Qinghua [VerfasserIn]
Zhou, Qiang [VerfasserIn]
Hu, Jianbing [VerfasserIn]
Weng, Jie [VerfasserIn]
Liu, Songlian [VerfasserIn]
Yin, Leilan [VerfasserIn]
Long, Ling [VerfasserIn]
Tong, Yajun [VerfasserIn]
Tang, Kewei [VerfasserIn]
Bai, Site [VerfasserIn]
Ou, Ludi [VerfasserIn]

Links:

Volltext

Themen:

Ag@ZnO NCs
Anticancer activity
Apoptosis
Crocus sativus
Cytotocicty
Journal Article

Anmerkungen:

Date Revised 02.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.jtemb.2024.127437

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370544153