Antiproliferative Activity of Selected Triterpene Acids from Rosemary on Metastatic Melanoma Cell Line WM-266-4

Suzana Isaković-Vidović; Barbara Dariš; Željko Knez; Kristina Vidović; Dejan Oprić; Polonca Ferk

doi:10.3889/oamjms.2021.6176

Authors

Suzana Isaković-Vidović Department of Radiology, Izola General Hospital, Izola, Slovenia; Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia https://orcid.org/0000-0001-7514-0137
Barbara Dariš Department of Pharmacology and Toxicology, Faculty of Medicine, Institute of Biomedical Sciences, University of Maribor, Maribor, Slovenia
Željko Knez Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia
Kristina Vidović Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Dejan Oprić Faculty of Medicine, Institute of Pathology, University of Belgrade, Belgrade, Serbia
Polonca Ferk Institute of Biostatistics and Medical Informatics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

DOI:

https://doi.org/10.3889/oamjms.2021.6176

Keywords:

Melanoma, Antiproliferative activity, Betulinic acid, Ursolic acid, Oleanolic acid

Abstract

BACKGROUND: Natural products and their derivatives, particularly secondary metabolites, have been recognized for many years as an important source of therapeutic agents. In this context, pentacyclic triterpene acids including betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) are highly valuable triterpenic acids because of their wide range of biological activities.

AIM: Therefore, the aim of our study was to investigate any potential effect of BA, UA, and OA on human melanoma WM-266-4 cells’ proliferation activity.

METHODS: BA, UA, and OA have been prepared in dimethyl sulfoxide in concentration range from 0.002 to 200 μM separately or in selected combination (UA+OA ratio 1:1 or 3.5:1), while cells in cell culture medium served as controls. The rapid colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was used to measure proliferation activity of the metastatic melanoma cell line WM-266-4 after being exposed to selected concentrations of BA, UA, OA, or UA+OA and during different time periods. Student’s t-test was used for single statistical comparisons. Data were analyzed using IBM SPSS 25.0 (IBM Corp., Armonk, NY). To account for multiple comparisons bias, p < 0.001 was considered statistically significant.

RESULTS: Our results showed decreased cell proliferation activity after 4 h of incubation of WM-266-4 cells with BA, UA, OA, and UA+OA. The highest inhibitory effect was noted when cells were incubated with selected triterpenic acids and both combinations of UA+OA during the incubation period of 48 h. When compared to control cells, concentration of 2 μM was the lowest concentration of BA that showed a significant decrease of the cells’ proliferation activity regardless the incubation period (4 h, 24 h, and 48 h) (p < 0.001).

CONCLUSION: Our encouraging results could be a good starting point for further studies on possible use of BA, UA, and OA in prevention and treatment of metastatic melanoma.

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