Differential Antioxidant Responses to Docetaxel, Berberine, and Their Combination in Normal and Cancerous Prostate Cells

One of the main causes of male death worldwide is prostate cancer (PC). The first-line treatment for advanced PC is docetaxel (DTX), where majority of patients develop drug resistance. Natural pharmeceuticals may pose a solution to lower side effects. Berberine (BBR) is a natural pentacyclic isoquinoline alkaloid with anticancer properties affecting cell signaling pathways and oxidative stress. Here, we compared the effects of DTX, BBR or their combination on PC3 and normal prostate stromal fibroblastic WPMY-1 cells to investigate different antioxidative cellular response to treatments. DTX and BBR+DTX adjuvant combination therapy significantly caused cytotoxic effects against both PC3 and WPMY-1 cells. BBR exerted cytotoxic effects to PC3 cancer cells but not normal cells. In normal cells, DTX up-regulated the malodialdehyde ((MDA) and glutathione peroxidase (GPx) levels but reduced the superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC) activities, BBR reduced MDA and TAC, elevated GPx while exerted almost no effect on SOD and CAT activities. The combination treatment highly and significantly elevated MDA, and markedly reduced all other parameters. DTX treatment of PC3 cancer cells decreased SOD, CAT, GPx, and TAC activities while increasing MDA. BBR treatment to PC3 cells reduced MDA, SOD, CAT, GPx but not TAC. The combination treatment to PC3 cells up-regulated MDA but reduced SOD, CAT, GPx and TAC activities. In conclusion, combining BBR and DTX in prostate cancer cells enhances oxidative stress, promoting apoptosis and reducing tumor viability. This combined effect may offer a promising treatment by maximizing anticancer efficacy while sparing healthy tissues.