Romanian Society of Pharmaceutical Sciences

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GENISTEIN AND QUERCETIN TRIGGER CYTOTOXICITY, APOPTOSIS, AND OXIDATIVE STRESS IN SK-MEL-28 CUTANEOUS MELANOMA CELLS

ANDREA ROMAN 1,2,#, IASMINA MARCOVICI 3,4,#, RAUL CHIOIBAȘ 2,5*, ANDREI MOTOC 2, GEORGE PUENEA 2, ZSOLT GYORI 2, ZORIN CRĂINICEANU 2, DIANA CAMELIA BONTE 2

1Faculty of Medicine, "Vasile Goldiș" Western University of Arad, 94 Revolutiei Blvd., 310130, Arad, Romania
2Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041, Timișoara, Romania
3Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041, Timișoara, Romania
4Research Centre for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041, Timișoara, Romania
5CBS Medcom Hospital, 12th Popa Sapca Street, 300047 Timisoara, Romania

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Cutaneous melanoma (CM) stands as one of the most aggressive cancers worldwide, presenting an alarming increase in the incidence rate and limited efficacious treatment options at present. Phytoestrogens, described as plant-derived compounds possessing an estrogen-like chemical structure, gained outstanding popularity due to their multispectral pharmacological effects. The current in vitro study aimed at a comparative screening of two bioactive phytoestrogens, genistein (GEN) and quercetin (QUE), as potential chemotherapeutics for CM prophylaxis and treatment. The results showed that both compounds exerted significant cytotoxicity in SK-MEL-28 CM cells at concentrations ranging between 50 and 200 μM, after 24 h of treatment, which was related to the ability of GEN and QUE to reduce cell viability, induce nuclear and cytoskeletal constriction, trigger apoptosis through caspase-9 activation, and generate intracellular oxidative stress. The cytopathic effect caused by GEN and QUE was stronger in SK-MEL-28 CM cells compared to HaCaT keratinocytes, suggesting a selective activity. However significant viability reduction was obtained for this healthy cell line as well at high concentrations after 24 hours of treatment. This study illustrated the anti-tumour effect of GEN and QUE and its underlying mechanisms, contributing to further investigations on their potential as therapeutics in CM prevention and treatment.