Cytotoxic and apoptotic effects of etoposide and ellagic acid alone or with possible synergistic/additive combinations on a canine D-17 osteosarcoma cell line

Ekren Asici Gs, F Kiral, A Bildik and Ulutas Pa
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Ekren Asici Gs: Department of Biochemistry, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkiye
F Kiral: Department of Biochemistry, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkiye
A Bildik: Department of Biochemistry, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkiye
Ulutas Pa: Department of Biochemistry, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkiye

Veterinární medicína, 2025, vol. 70, issue 8, 279-293

Abstract: Osteosarcoma (OSA) is the most prevalent and aggressive malignancy of canine bones. Etoposide is an effective chemotherapeutic agent for cancer treatment, whereas ellagic acid is a naturally occurring compound with antioxidant and anticancer properties; however, both are inhibitors of the topoisomerase enzyme. In this study, the synergistic/additive effect of etoposide, known to have a growth-inhibitory impact in canine osteosarcoma (OSA) cells, and ellagic acid was investigated. The mechanism by which this effect inhibits cell growth at lower etoposide doses was also examined. The IC₅₀ values of both agents were determined, and possible combination doses were generated accordingly and applied to canine OSA cells. The apoptotic effects of the combinations were evaluated based on DNA breaks and the activity levels of caspase 3, 8, and 9. These findings were supported by the expression levels of Bcl-2, Bax, and Bid genes, as well as the AO/EtBr staining method. The effects on cell cycle and proliferation were analysed through survivin and NF-κβ gene expressions. Antimetastatic effects were determined using invasion and migration assays. EA is a potential therapeutic agent for cancer treatment. In combination with ET, a higher anticancer efficacy was demonstrated compared to etoposide alone. Potential treatment side effects can be reduced by enabling the use of lower drug doses.

Keywords: acridine orange/ethidium bromide staining; Bax/Bcl-2 ratio; caspase; 3; 8; 9 (search for similar items in EconPapers)
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:caa:jnlvet:v:70:y:2025:i:8:id:24-2025-vetmed

DOI: 10.17221/24/2025-VETMED

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