Stachydrine hydrochloride induces cell senescence and ferroptosis of castration-resistant prostate cancer

Paclitaxel resistance of castration-resistant prostate cancer (CRPC) remains a substantial challenge in clinical oncology. Our investigation aimed to explore the potential of stachydrine hydrochloride in addressing paclitaxel resistance within CRPC. Parental prostate cancer cells, PC3 and DU145, and the corresponding paclitaxel-resistant counterparts, PC3-TxR and DU145-TxR, were subjected to indicated concentrations to determine the IC50 of paclitaxel and stachydrine hydrochloride. Cell viability and proliferation were evaluated by MTT and colony formation assays. Stachydrine hydrochloride-mediated apoptosis, senescence, and ferroptosis were detected using Western blot, SA-β-gal staining, and QuantiChrom iron assay. We found a pronounced reduction in paclitaxel resistance in both PC3-TxR and DU145-TxR cells following exposure to stachydrine hydrochloride. The considerable decrease in paclitaxel's IC50 values in these cells highlights the potential of stachydrine hydrochloride in sensitizing CRPC cells to paclitaxel-based therapies. Mechanistically, stachydrine hydrochloride treatment significantly upregulated the expression of estrogen receptor beta (ERβ) and promoted cell apoptosis, senescence, and ferroptosis pathways in CRPC. Our study provides promising insights into the potential of stachydrine hydrochloride as a novel therapeutic adjunct in overcoming paclitaxel resistance in CRPC.