A novel Rhein derivative AQ-NC inhibits prostate cancer by suppressing the PI3K/AKT pathway.

[OBJECTIVE] This research endeavors to explore the anti-prostate cancer (PCa) activity and potential molecular mechanisms of the newly synthesized Rhein derivative AQ-NC.

[METHODS] The CCK-8 test was employed to evaluate the anti-PCa activity of AQ-NC and its lead compound, Rhein. The EdU assay was utilized to assess how AQ-NC impacts the proliferation of PCa cells. The scratch and Transwell assays were carried out to detect the influence of AQ-NC on the migratory capacity of DU-145 and C4-2 cells. Western blot analysis was used to measure the expression of proteins associated with migration. Flow cytometry was applied to detect the effect of AQ-NC on apoptosis in DU-145 and C4-2 cells. Additionally, the expression levels of apoptosis-associated proteins were assessed using Western blot. Mechanistically, potential signaling pathways were predicted by molecular docking and the expression of relevant proteins were verified using Western Blot.

[RESULTS] AQ-NC demonstrated significantly superior cellular activity to Rhein, as determined by the CCK-8 assay. Observations of cell morphology and EdU assays further demonstrated that AQ-NC could suppress the proliferation of PCa cells. Scratch and Transwell assays revealed that AQ-NC effectively hindered the migration of PCa cells. Flow cytometry and Western blot analyses indicated that AQ-NC could trigger apoptosis in PCa cells. Additionally, molecular docking and Western blot results indicated that AQ-NC could suppress the expression of proteins related to p-EGFR, p-PI3K, and p-AKT.

[CONCLUSION] AQ-NC inhibits the proliferation and migration of PCa cells and induces apoptosis, potentially through the inhibition of the PI3K/AKT signaling pathway.