Romanian Society of Pharmaceutical Sciences

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GENISTEIN−QUERCETIN COMBINATORIAL TREATMENT YIELDS ENHANCED ANTICANCER ACTIVITY IN A-431 AND A-375 HUMAN SKIN CANCER CELLS

ANDREA ROMAN 1,2#, CASIANA BORU 1#, ANDRADA IFTODE 3,4,5*, ANDREEA SMEU 3,4,5, MIHAELA BOȚA 3, LAVINIA VLAIA 3, DANIELA SAȘCO 3,4, MIRELA NICOLOV 3, DAN ILIESCU 6

1 Faculty of Medicine, “Vasile Goldiș” Western University of Arad, 94 Revoluției Blvd., 310130 Arad, Romania
2 Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
3 Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timișoara, 2nd Eftimie Murgu Square, RO-300041 Timișoara, Romania
4 Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041, Timișoara, Romania
5 University Clinic of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timișoara, Romania
6 University Clinic of Surgical Semiology I and Thoracic Surgery, Faculty of Medicine, “Victor Babeș” University of Timișoara, 2 Eftimie Murgu Square, 300041 Timișoara, Romania

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Skin cancer is a malignant tumour that develops from skin cells and is recognised as one of the most prevalent cancers worldwide. Skin cancer is divided into non-melanoma skin cancer and melanoma, both types requiring advances or alternatives to conventional treatments due to the limitations imposed by them (e.g., drug resistance, toxic effects). The purpose of the present work was to evaluate a natural combinatorial strategy between genistein (GEN) and quercetin (QUE) as an alternative treatment in skin cancer, using two distinct cell lines as experimental models: A-431 (epidermoid carcinoma) and A-375 (malignant melanoma). The results showed that the combinatorial GEN-QUE treatment induced a superior cytotoxicity compared to single agent treatment, characterised by lower cell viability when the associative treatment was applied (reaching up to 23.07% for A431 and 38.43% for A375), decreased cell confluency, induced more prominent nuclear changes (chromatin condensation, nuclear shrinkage) and mitochondrial changes (condensation) when treated with GEN and QUE. These novel findings support the improved anticancer ability of natural compounds when used in combinatorial treatments, emphasising the therapeutic potential in non-melanoma and melanoma skin cancers.