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MYRICETIN-FISETIN COMBINATORIAL TREATMENT AS A POTENTIAL STRATEGY FOR CUTANEOUS MELANOMA – AN IN VITRO STUDY

CRISTINA GROSU (DUMITRESCU) 1,2#, MIHAELA BOȚA 3#, DIANA BONȚE 4*, CLAUDIA TOMA 5, ANDREEA SMEU 1,2, LAVINIA VLAIA 3, CASIANA BORU 5

1 Discipline of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
2 Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
3 Department II-Pharmaceutical Technology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4 Discipline of Biochemistry, Department IV, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania
5 “Vasile Goldiș” Western University of Arad, Romania, 86 Liviu Rebreanu Street, 310048, Arad, Romania

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Cutaneous melanoma (CM) is a global health challenge with an increasing incidence risk. Conventional treatments include chemotherapy, specific surgeries, radiotherapy or immunotherapy, but in recent decades it has been observed that these treatment options display several limitations (e.g. toxic effects or treatment resistance). Botanical compounds and, in particular, the class of flavonoids are versatile agents with manifold biological activities recognised in the medico-pharmaceutical domain, among which myricetin and fisetin are acknowledged, two phytocompounds that have proven their potential in the treatment of CM through their antiproliferative and pro-apoptotic effects. Given these aspects, the present work aims to explore MYR and FIS and their combinatorial treatment in the CM cell line B164a5 and healthy JB6 Cl 41-5a cells. The results revealed that the two compounds possessed promising activity in inhibiting B164a5 cells, and the combination of MYR+FIS exerted superior effects compared to individual treatment of the agents by decreasing cell viability, inducing cell dysmorphology, reducing cell number, producing apoptotic-like nuclei and mitochondrial damage. Furthermore, the results suggested that the association between the two compounds was selective, avoiding damage to normal epidermal cells.