Romanian Society of Pharmaceutical Sciences
 

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IN VITRO INSIGHTS REGARDING THE ROLE OF MELANIN IN MELANOMA CELLS’ RESPONSE TO BETULINIC ACID TREATMENT

LAVINIA MELANIA BRATU 1#, IASMINA MARCOVICI 2,3#, IOANA MACASOI 2,3, ANIKO
MANEA 1*, BOGDAN NICULESCU 4#, FLAVIUS OLARU 1, ALINA HEGHES 2, CRISTINA DEHELEAN 2,3, DORINA CORICOVAC 2,3

1Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
2Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
3Research Centre for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4Department of Sports and Health, “Constantin Brancuși” University, 210152, Târgu Jiu, Romania

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Malignant melanoma (MM), the cancer arising from the normal-to-malignant switch of melanocytes, remains the most aggressive type of skin cancer with an annual increasing incidence worldwide. Based on the presence or absence of melanin, MM is divided in melanotic (pigmented) or amelanotic (non-pigmented) melanoma. Melanin is the natural pigment providing a protective role against harmful ultraviolet (UV) radiations and oxidative stress to epidermal melanocytes and surrounding keratinocytes. Recent studies reveal the ability of melanin to bind drugs via covalent and non-covalent bonds, leading to their accumulation within pigmented tissues which might influence the response of MM to chemotherapy. Betulinic acid (BA) is a pentacyclic triterpenoid possessing a multitude of therapeutic properties, including antimelanoma activity. The present study aimed to investigate the response of two MM cell lines to the antitumour effect of BA, considering their melanin content and to evaluate the cytotoxic potential of BA in healthy primary fibroblasts. The results reveal a dose-dependent decrease in the viability and confluence of all cell lines. However, SK-MEL-5 cells (IC50 =13.67 µM for 24 h, and 7.48 µM for 72 h) exerted a higher sensitivity to BA when compared to B16-F10 cells (IC50 = 52.12 µM for 24 h, and 25.54 for 72 h). BA induces a differential cytotoxicity in healthy, MM non-pigmented SK-MEL-5 and pigmented B16-F10 cells. Therefore, further studies are required to confirm the interaction between BA and melanin.