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

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. RezumatMelanomul cutanat (CM) reprezint o provocare pentru sntatea mondial, cu un risc de inciden n cretere.Tratamentele convenionale includ chimioterapia, operaii chirurgicale specifice, radioterapia sau imunoterapia, dar n ultimele decenii s-a observat c aceste opiuni de tratament prezint mai multe limitri (de exemplu, efecte toxice sau rezisten la tratament).Compuii botanici i n special clasa flavonoidelor sunt ageni versatili, cu multiple activiti biologice recunoscute n domeniul medicofarmaceutic, printre care sunt miricetina (MYR) i fisetina (FIS), doi fitocompui care i-au dovedit potenialul n tratamentul CM prin efectele lor antiproliferative i pro-apoptotice.Avnd n vedere aceste aspecte, lucrarea de fa i propune s exploreze MYR i FIS i tratamentul lor combinatorial n linia celular de CM B164a5 i asupra celulelor sntoase JB6 Cl 41-5a.Rezultatele au artat c cei doi compui posed o activitate promitoare n inhibarea celulelor B164a5, iar combinaia MYR+FIS a exercitat efecte superioare comparativ cu tratamentul individual al agenilor prin scderea viabilitii celulare, inducerea dismorfologiei celulare, reducerea numrului de celule, producerea de nuclee de tip apoptotic i deteriorarea mitocondrial.n plus, rezultatele au sugerat c asocierea dintre cei doi compui a fost selectiv, evitnd deteriorarea celulelor epidermiale normale.