Romanian Society of Pharmaceutical Sciences
 

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BETULIN INDUCES CYTOTOXIC EFFECTS IN AN OSTEOSARCOMA CELL LINE

IOAN SMULTEA 1,2, ȘTEFANIA-IRINA DUMITREL 1,2,3#, JENEL MARIAN PĂTRAȘCU 4*, DANIELA SAȘCO 1,2, CASIANA BORU 5,⁶

¹ Doctoral School, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
2 Research Centre for Pharmaco-Toxicological Evaluations, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
3 Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4 Department of Orthopedics-Traumatology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timișoara, Romania
5 Department of Medicine, University of Medicine and Pharmacy “Vasile Goldis”, 310045 Arad, Romania
6 Arad County Emergency Clinical Hospital, 310037 Arad, Romania

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Although advances in multimodal chemotherapy and oncological surgery have improved outcomes in osteosarcoma (OS), prognosis remains poor for patients with metastatic or treatment-resistant disease. Natural compounds, including betulin (BET), a pentacyclic triterpenoid, have attracted interest for their anticancer properties. Based on these considerations, the main objective of this study was to evaluate the in vitro cytotoxicity of BET on the human OS cell line U-2 OS. Following 24 h of BET treatment (10 - 50 µM), cell viability decreased in a dose-dependent manner relative to untreated controls (p < 0.0001). JC-1 staining showed reduced red/green fluorescence ratios, consistent with mitochondrial membrane depolarization (p < 0.001 and p < 0.0001). Microscopy revealed nuclear and mitochondrial morphological alterations, while AO/PI staining showed increased PI-positive cells at all BET concentrations. These findings indicate that BET reduces U-2 OS cell viability and is associated with mitochondrial and cell death-related morphological changes.