Synthesis of a niosome-based drug delivery system containing Sambucus ebulus extract: evaluation of its pro-apoptotic and anti-metastatic effects on HeLa cervical cancer cells

Kavousi, Mahsa; Aliasgari, Elahe; Bakhtiari, Marjan

doi:10.22038/ajp.2026.27992

Synthesis of a niosome-based drug delivery system containing Sambucus ebulus extract: evaluation of its pro-apoptotic and anti-metastatic effects on HeLa cervical cancer cells

Articles in Press

Document Type : Original Research Article

Authors

Department of Biology, ET.C., Islamic Azad University, Tehran, Iran

10.22038/ajp.2026.27992

Abstract

Objective: Cervical cancer affects over half a million women annually. Given the increasing interest in natural compounds as therapeutic agents, this study investigates the apoptotic and anti-metastatic effects of Sambucus ebulus extract—a medicinal plant with antioxidant and cytotoxic properties—encapsulated in niosomes on HeLa cervical cancer cells. Encapsulation in niosomes enhances the stability and cellular delivery of the extract, potentially improving its therapeutic efficacy.
Materials and Methods: Ethanolic extract of S. ebulus was prepared using Soxhlet extraction, followed by niosome synthesis and encapsulation of the extract. The physicochemical characterization of niosomes was performed using FTIR, DLS, and SEM analysis. Cytotoxicity of free niosomes, free extract, and loaded niosomes was assessed via MTT assay at 24, 48, and 72 hr. Cell cycle was analyzed using flow cytometry, while changes in CASP8, CASP3, MMP2 and MMP9 gene expression were evaluated through real-time PCR.
Results: The mean size of synthesized niosomes was 366 nm. The MTT assay revealed that S. ebulus extract-loaded niosomes exerted the highest cytotoxic effect on HeLa cells, whereas no significant cytotoxicity was observed in the HOSEpiC normal cell line. Real-Time PCR showed a significant upregulation of apoptotic genes (CASP3, p<0.001; CASP8, p<0.01) and a downregulation of metastatic genes (MMP2, MMP9, p<0.01). Flow cytometry indicated that treatment with S. ebulus extract-loaded niosomes induced 50.09% total apoptosis (p<0.01), the highest among the tested groups. Cell cycle analysis demonstrated G0/G1 phase arrest at 24 hr treatment. Scratch assay confirmed a significant inhibition of cancer cell migration.
Conclusion: Encapsulation of S. ebulus within niosomes enhances the targeted delivery and efficacy of S. ebulus extract. Its apoptotic and anti-metastatic effects suggest potential for investigation as a novel therapeutic approach against cervical cancer.

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