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EVALUATION OF OLEANOLIC ACID, DOXORUBICIN AND THEIR ASSOCIATION IN THE TREATMENT OF MELANOMA: ENHANCED EFFICACY AND ANTIANGIOGENIC POTENTIAL

GEORGE PUENEA 1#, BOGDAN ALMĂJAN-GUȚĂ 2#, RAUL CHIOIBAȘ 1*, IOANA MACAȘOI 3,4, ANDREEA GEAMANTAN 3,4, ȘTEFANIA DINU 5,6, PETRU MERGHEȘ 7, EUGEN RADU BOIA 1, ALINA ANDREEA TISCHER 1, ANDRADA IFTODE 3,4

1Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
2Faculty of Physical Education and Sport, West University of Timișoara, Vasile Pârvan Boulevard 4, 300223, Timișoara, Romania
3Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4Research Centre for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
5Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, 9 Revoluției 1989 Boulevard, 300070, Timișoara, Romania
6Paediatric Dentistry Research Centre, Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, 9 Revoluției 1989 Boulevard, 300041, Timișoara, Romania
7Department of Physical Education and Sport, “King Michael I” University of Life Sciences from Timișoara, 119 Calea Aradului Street, Timișoara, Romania

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As one of the most aggressive types of skin cancer, melanoma, remains a challenging malignancy to treat, necessitating continued research for more effective therapeutic approaches. This study examined the impact of oleanolic acid and doxorubicin individually and in combination on the viability of cells, morphological changes and antiangiogenic properties. Oleanolic acid, doxorubicin and a combination of both were used to treat melanoma cells - A375. The viability of the cells was assessed using MTT assay, and phase-contrast microscopy was used to observe morphological changes. To assess apoptotic alterations in the nuclei, Hoechst 33342 staining was applied to the nuclei. The antiangiogenic potential was evaluated using the hen's egg chorioallantoic membrane as a biological model. Cell viability was significantly reduced by both oleanolic acid and doxorubicin while cell morphology revealed distinct changes in shape and adherence, which are common to apoptotic processes. Apoptosis was confirmed as the underlying mechanism by the presence of condensation and fragmentation of the nuclei. It should be noted that the combination of oleanolic acid and doxorubicin had a more pronounced effect on cell viability and morphological changes associated with apoptosis. Furthermore, the assessment of antiangiogenic potential demonstrated that oleanolic acid, along with doxorubicin, was capable to inhibit the formation of new blood vessels. According to this study, both oleanolic acid and doxorubicin exhibit promising anti-melanoma properties, including a reduction in cell viability and induction of apoptosis. These effects are enhanced by their association, indicating a potential synergistic effect. A valuable insight has been gained into the therapeutic potential of combining oleanolic acid and doxorubicin in the treatment of melanoma in the present study. Efforts should be made to elucidate the underlying mechanisms of action of this combination as well as evaluate its safety and efficacy in preclinical and clinical settings to improve therapeutic outcomes.