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Unveiling the Anti-cancer Potential of Vulpinic Acid: A Selective Therapeutic Agent Against Oral Squamous Cell
Dilara Nur Şengüm1, Ayşe Hale Alkan2, Fatma Zeynep Bozkurt2
1Department of Oral and Maxillofacial Surgery, Ankara University Faculty of Dentistry, Ankara, Türkiye.
Introduction:
Lip and oral cavity cancers are among the most common types of cancer worldwide and remain a major health problem due to poor prognosis and treatment- related side effects. Therefore, identifying new naturally derived compounds with selective cytotoxic effects on oral cancer cells is essential. Vulpinic acid, a lichenderived secondary metabolite, has shown antioxidant and anticancer activities in various cancer types. However, its effects on oral cancer cells have not yet been clarified. This study aims to investigate the cytotoxic and apoptotic effects of vulpinic acid on oral cancer cells and to explore its possible molecular mechanisms.
Methods:
The cytotoxic effect of vulpinic acid on OSC-19 oral cancer and MRC-5 normal fibroblast cells was assessed using xCELLigence analysis. The impact of vulpinic acid on cell cycle progression, apoptotic mechanisms, colony formation, wound healing, and molecular-level effects was analyzed using flow cytometry, mitochondrial membrane potential assay, and qRT-PCR. The effect of vulpinic acid on BIRC5 protein levels was further confirmed by western blot analysis.
Results:
The results showed that the IC50 value of vulpinic acid was 59 μM in OSC-19 cells and 114 μM in MRC-5 cells, demonstrating its selective cytotoxic effect on oral cancer cells. Vulpinic acid treatment suppressed colony formation by 55.5% and reduced cell migration by 71.2-fold at 96 h. Cell cycle analysis revealed that vulpinic acid induced G1 phase arrest, while apoptosis analysis showed a decrease in mitochondrial membrane potential. qRT-PCR analysis revealed an upregulation of pro-apoptotic genes (BID, CASP4, CASP7, BAK1, BCL2L2) and downregulation of the anti-apoptotic gene survivin (BIRC5). According to western blot analysis, BIRC5 protein expression decreased 2.39-fold following vulpinic acid treatment.
Discussion:
These findings indicate that vulpinic acid has the potential to be considered as an anti-cancer agent.
Conclusion:
Further in vivo and clinical studies are required to validate its therapeutic efficacy and safety profile.
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