SYNERGISTIC ANTICANCER EFFECTS OF CISPLATIN AND POMEGRANATE EXTRACT IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

Keywords:  Head and neck squamous cell carcinoma; HNSCC; pomegranate; punica granatum; natural extract; cisplatin

Abstract:
Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks among the most common malignancies worldwide [1]. Cisplatin (CIS), a conventional chemotherapeutic agent, is limited by severe adverse effects [2]. Pomegranate extract (PE), a natural compound, has demonstrated antitumor potential with a favorable safety profile [3,4]. This study aimed to evaluate the cytotoxic, antiproliferative, and apoptotic effects of CIS and PE, individually and in combination, on HNSCC HEP2 cells.

Materials and Methods: Cells were divided into four groups: control, CIS-treated, PE-treated, and CIS-PE combination. Cytotoxicity was assessed using the MTT assay to determine IC50 values. Morphological alterations were evaluated histologically. Immunocytochemistry was used to assess Ki67 and Bcl-2 expression. Gene expression levels of Ki67 and Bcl-2 were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Data were analyzed using one-way ANOVA followed by Bonferroni post hoc tests, with significance set at p < 0.05.

Results: The CIS-PE group exhibited the highest cytotoxicity and the most pronounced morphological degeneration. Immunocytochemical analysis revealed significantly reduced Ki67 and Bcl-2 expression in all treatment groups compared to control (p < 0.001), with the CIS-PE group showing the lowest levels (Ki67: 15.9 ± 3.2%, Bcl-2: 8.1 ± 6.3%; p < 0.001). Similarly, RT-qPCR confirmed significant downregulation of Ki67 and Bcl-2 gene expression, particularly in the CIS-PE group (Ki67 fold change: 36.5 ± 0.32, Bcl-2: 24.4 ± 0.09; p < 0.001), indicating a strong synergistic effect (Figure 1).

Conclusion: These findings suggest that PE has cytotoxic, antiproliferative, and pro-apoptotic effects on HEP2 cells, and its combination with CIS enhances therapeutic efficacy through a synergistic interaction. With its potential to improve outcomes and reduce toxicity, PE represents a promising adjuvant to conventional chemotherapy, warranting further investigation into its mechanisms and future clinical applications in HNSCC therapy.

Figure 1: Comparative analysis of Ki67 and Bcl-2 expression in HEp-2 cells across different groups showing marked reduction is observed in both markers following PE, CIS, and particularly combined CIS-PE treatment.

References:
[1] Johnson D. E. et al. (2020) Nat. Rev. Dis. Prim., 6, 92. [2] Waissbluth S. and Daniel S. J. (2013) Hear. Res., 299, 37–45. [3] Rahmani A. H. et al. (2017) Pharmacogn. J., 9, 689–695. [4] Sharma P. et al. (2017) Molecules, 22, 177.

Biography: Dr. Safaa Baz is an Assistant Professor of Oral Pathology at the British University in Egypt. She earned her PhD from Cairo University in 2020 with top distinction and has over a decade of experience in academic teaching, research, and oral cancer diagnostics. Dr. Baz has published extensively in indexed peer-reviewed journals, presented at international conferences, and is the recipient of multiple awards, including the YIRG and ICG grants. Her research interests include oral cancer, oral diseases, cancer therapeutics, nanotoxicology, and the diagnostic and therapeutic applications of natural compounds and molecular biomarkers.

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