Romanian Society of Pharmaceutical Sciences
 

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COMBINED CYTOTOXIC EFFECTS OF FISETIN AND GENISTEIN IN DETROIT-562 PHARYNGEAL CARCINOMA CELLS

MHD KHER ALSAEYD AHMAD 1#, DOINA CHIORAN 2#, RALUCA-ADRIANA MILUTINOVICI 3,4*, DIANA HAJ ALI 5,6,7, MIHAELA IULIANA SIRBU (CIORTAN) 5,8, RAMONA AMINA POPOVICI 9 , ȘTEFANIA DINU 10,11, CAMELIA SZUHANEK 4, MIHAELA CRISTINA NEGRU 8, ANDREEA- MIHAELA KIȘ 9

1 Doctoral School of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, 9 Revolutiei 1989 Ave., 300070 Timisoara, Romania
2 Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 9 Revolutiei 1989 Ave., 300070 Timisoara, Romania
3 Department of Orthodontics, Faculty of Dental Medicine, Victor Babeș University of Medicine and Pharmacy, 9 Revolutiei 1989 Ave., 300070 Timisoara, Romania
4 Research Center “Ortho-Center”, Faculty of Dental Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, 9 Revoluției din 1989 Ave., 300041 Timisoara, Romania
5 Doctoral School, “Victor Babes” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
6 Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2nd Eftimie Murgu Square, 300041 Timișoara, Romania
7 Research Center for Pharmaco-Toxicological Evaluations, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2nd Eftimie Murgu Square, 300041 Timișoara, Romania
8 Department of Ear, Nose and Throat, Faculty of Medicine, "Victor Babeș" University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
9 Department of Management and Communication in Dental Medicine, Department I, Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, 300041 Timișoara, Romania
10 Department of Pedodontics, Faculty of Dental Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, 9 Revolutiei 1989 Ave., 300070 Timisoara, Romania
11 Pediatric Dentistry Research Center, Faculty of Dental Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, 9 Revolutiei 1989 Ave., 300070 Timisoara, Romania

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Pharyngeal cancer is one of the most aggressive malignancies, often diagnosed at advanced stages, with current therapeutic options facing significant limitations in terms of efficacy and tolerability. Therefore, natural compounds, often characterized by a more favorable safety profile, could represent a promising option in the therapeutic management of this disease. In this context, the present study evaluated the cytotoxic potential of two flavonoids, fisetin (FIS) and genistein (GEN), and their combination on a 2D pharyngeal cancer cell model, Detroit-562. The study included an analysis of cell viability using the MTT assay and LDH release, followed by assessment of cell morphology and essential organelles, such as the nuclei and mitochon- dria, and evaluation of pro-apoptotic and necrotic effects via AO/PI double staining. In addition, the combination’s irritant potential was analyzed in the HET-CAM in ovo model. The results showed that, across all assays, the combinatorial treatment exhibited higher cytotoxicity without causing an irritant effect on the vascular plexus, supporting its potential use as an adjuvant therapy for the treatment of pharyngeal cancer.