Modulation of apoptotic pathways and epithelial–mesenchymal transition in HeLa cervical cancer cells by Ficus deltoidea-silver nanoparticles (FD-AgNPs)

Open

Happy Kurnia Permatasari, Raisha Anis Fatiha, Christian Kencana Ngabdi, Jihan Salwa Azizah, Bayu Lestari, Soon Wei To, Nik Ahmad Nizam Nik Malek

2026 Phytomedicine Plus Vol. 6 Issue 1 Article Cited by 2

Abstract

Cervical cancer, primarily caused by persistent Human Papillomavirus (HPV) infection, is a leading cause of cancer-related mortality due to its propensity for resistance and metastasis. Ficus deltoidea, a medicinal plant rich in flavonoids and polyphenols, has demonstrated promising anticancer properties when formulated into silver nanoparticles. This study aimed to investigate the proapoptotic and antimetastatic effects of Ficus deltoidea-Silver Nanoparticles (FD-AgNPs) in HeLa cervical cancer cells. Cells were treated with FD-AgNPs at concentrations of 2.5, 5, and 10 μg/mL, with cisplatin 2.5 μg/mL as a positive control and a negative control group. Cell viability and apoptosis were evaluated using trypan blue and flow cytometry, while antimetastatic effects were assessed via a wound-healing assay and immunofluorescent detection of Epithelial-Mesenchymal Transition (EMT) markers, such as Snail and vimentin. Results showed that FD-AgNPs significantly reduced HeLa cell viability (p = 0.0004) and increased apoptosis (p < 0.0001) in a dose-dependent manner. The highest concentration significantly inhibited cell migration compared to cisplatin (p < 0.001), downregulated Snail (p < 0.0001) and vimentin (p < 0.001), indicating EMT suppression. These findings highlight the dual action of FD-AgNPs in inducing apoptosis and inhibiting EMT-driven metastasis, supporting their potential as a safe and effective complementary therapy for cervical cancer. © 2025 The Author(s)

Affiliations

Biochemistry and Biomolecular Department, Faculty of Medicine, Brawijaya University, Malang, 65145, Indonesia; Biomedical Science Master's Program, Faculty of Medicine, Brawijaya University, Malang, 65145, Indonesia; Pharmacology Department, Faculty of Medicine, Brawijaya University, Malang, 65145, Indonesia; Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Johor, 81310, Malaysia; Centre for Sustainable Nanomaterials (CSNano), Ibnu Sina Institute for Scientific and Industrial Research (ISI-ISIR), Universiti Teknologi Malaysia, Johor, 81310, Malaysia