Document Type : Original Article
Authors
1
Lecturer, Oral Pathology Department, Faculty of Dentistry, The British University in Egypt,
2
Lecturer of Oral Biology, Faculty of Dentistry, Fayoum University, El Fayoum, Egypt,
3
Lecturer of oral and Maxillofacial pathology, Faculty of Dentistry, Cairo University, Giza, Egypt
Abstract
Background: Patients with head and neck squamous cell carcinoma (HNSCC) suffer from poor prognosis despite advancements, primarily due to toxicity and resistance associated with conventional chemotherapeutics such as cisplatin (CDDP). Graviola extract (GE), also known as Annona muricata, is a natural compound with anticancer properties and favorable safety profile. This in vitro study aimed to investigate the cytotoxic, antiproliferative, and pro-apoptotic potential of GE, CDDP, and their combination (CDDP+GE) on HEp-2 cells derived from HNSCC.
Methods: Cytotoxicity was assessed using MTT assay, and IC50 values were determined for the GE, CDDP, and CDDP+GE treatment groups compared to the untreated control. HEp-2 cells were subsequently treated with the predetermined IC50 doses for further investigations. Immunocytochemistry and RT-qPCR were conducted to evaluate the expression of Ki-67 and Bcl-2. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post-hoc test, with significance set at p 0.05.
Results: All treatment groups significantly reduced HEp-2 cells viability compared to the control (p < 0.0001). The combination group (CDDP+GE) exhibited enhanced cytotoxicity (IC50 = 28.47 ± 0.03 µg/mL) compared to GE alone (73.99 ± 0.29 µg/mL) or CDDP alone (2.88 ± 0.30 µg/mL). Immunocytochemical and gene expression analyses revealed decreased Ki-67 and Bcl-2 expression across all treated groups, with the lowest levels observed in the CDDP+GE group (p < 0.0001), indicating synergistic and antiproliferative and pro-apoptotic effects.
Conclusions: GE combined with CDDP offers strong antiproliferative and apoptotic effects on HEp-2 cells, indicating its potential as an adjunct or alternative treatment for HNSCC.
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