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

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. RezumatCancerul de piele este o tumor malign care se dezvolt din celulele pielii i este recunoscut ca fiind unul dintre cele mai rspndite cancere la nivel mondial.Cancerul de piele se mparte n cancer de piele non -melanom i melanom, ambele tipuri necesitnd progrese sau alternative la tratamentele convenionale din cauza limitrilor impuse de acestea (de exemplu rezisten la medicamente, efecte toxice).Scopul prezentei lucrri a fost de a evalua o strategie combinatorie natural ntre genistein (GEN) i quercetin (QUE) ca tratament alternativ n cancerul de piele, folosind dou linii celulare distincte ca modele experimentale: A-431 i A-375.Rezultatele au artat c tratamentul combinatorial GEN-QUE induce o citotoxicitate superioar tratamentului cu un singur agent, caracterizat printr-o viabilitate celular mai sczut atunci cnd se aplic tratamentul asociativ (ajungnd pn la 23,07% pentru A431 i 38,43% pentru A375), confluen celular mai sczut, modificri nucleare (condensarea cromatinei, micorarea nucleelor) i modificri mitocondriale mai proeminente (condensare) n cazul tratamentului cu GEN i QUE.Aceste rezultate noi susin capacitatea anticanceroas mbuntit a compuilor naturali atunci cnd sunt utilizai n tratamente combinatorii, subliniind potenialul terapeutic n cancerul de piele non-melanom i melanom.