Akademik Veri Yönetim Sistemi
X. Multidisciplinary Cancer Research Congress, Eskişehir, Türkiye, 8 - 11 Mayıs 2025, ss.199, (Özet Bildiri)
Introduction and Aim: Current chemotherapy treatments for ovarian cancer primarily utilize cisplatin and carboplatin, which are often associated with the development of therapy resistance. Recently, palladium (Pd) complexes have attracted attention due to their higher solubility and less kidney toxicity, compared to platinum analogs. This study focuses on exploring the anti-cancer potential of a palladium complex, [Pd(bpma)(barb)Cl]‧H2O, on ovarian cancer cell lines and uncovering the potential mechanisms involved.
Materials and Methods: SRB and MTT assays were performed on three high-grade serous ovarian cancer cell lines (CaOv-3, Kuramochi, and Ovsaho) at concentrations ranging from 1 nM to 100 μM after 48h treatment. Morphological and biochemical evaluation of cell death modality was performed with fluorescent staining and flow cytometry, respectively. Cellular DNA damage, oxidative stress and cell cyle progression were analyzed with flow cytometry. Cell migration was quantified using the scratch assay (wound healing assay). Gene expression analysis via qPCR was conducted to further characterize the biological response to the treatment.
Results: The Pd complex has cytotoxic and growth inhibitory effect on particularly Ovsaho cells, with 13 μM IC50 which was dramatically lower then that of cisplatin. This complex appears to induce apoptosis through mechanisms involving acumulation of ROS that triggers DNA damage which is reversed by sequencial treatment of N- acetylcysteine (NAC). Gene expression profile showed the upregulation of cell cyle related genes CDC20, CDC25A; DNA damage related gene GADD45A; oxidative stress related genes NOX1, SOD1 and proapoptotic genes HRK, NOXA, PUMA, DR5. Taken together, the results suggest that Pd complex causes oxidative stress leading to DNA damage-mediated cell cycle arrest and apoptotic cell death.
Conclusion: Our palladium complex is a promising therapeutic agent for a specific subtype (Ovsaho) of ovarian cancer, which deserves further attention for in vivo proof-of-concept studies.