Abstract
Introduction: Prostate adenocarcinoma is commonly treated with radiation and chemotherapy, but resistance and toxicity limit their success, highlighting the need for novel radiosensitizers. We investigated the effects of 7-Geranyloxycoumarin, alone and in combination with radiation, on the expression of β-catenin (CTNNB1), c-MYC, and Gankyrin (PSMD10), key mediators of Wnt signaling pathway associated with radioresistance in prostate adenocarcinoma cells.
Methods: STRING and GEPIA2 were used for interactome mapping, pathway enrichment, and expression/survival validation in prostate adenocarcinoma. Human prostate adenocarcinoma (PC-3) cells were pretreated with 40 µM 7-Geranyloxycoumarin and subsequently irradiated with 4 Gy. Gene expression was assessed by real-time PCR after 72 h.
Results: In silico analyses confirmed interactions among CTNNB1, c-MYC, and PSMD10, their involvement in the Wnt pathway, and the overexpression and prognostic trends of c-MYC and PSMD10. In PC-3 cells, 7-Geranyloxycoumarin treatment significantly decreased c-MYC expression (P<0.0001), while the combined treatment increased CTNNB1 (P<0.01) but decreased PSMD10 and c-MYC, indicating disruption of Wnt pathway.
Conclusion: 7-Geranyloxycoumarin modulates the Wnt signaling pathway by suppressing the expression of CTNNB1, c-MYC, and PSMD10, key mediators of this pathway, thereby enhancing radiosensitivity and highlighting its potential as an adjuvant therapy in prostate adenocarcinoma.