Abstract
OBJECTIVES: There is a considerable interest in combination therapy targeting the complex interlinked pathways in prostate cancer due to the development of drug resistance with monotherapies. A standardized fraction of Bacopa monnieri CDRI-08 was developed and patented by the Central Drug Research Institute (CDRI), Lucknow, for the treatment of neurodegenerative diseases. Recent studies with the plant and its phytocompounds have shown effective anticancer and antioxidant activity. Therefore, in the current research, the combined effect of Abiraterone acetate (AA) and CDRI-08 was studied in androgen-independent prostate cancer cells in vitro. MATERIALS AND METHODS: Initially, the in vivo toxicity of CDRI-08 was studied in zebrafish embryos. In vitro individual cytotoxicity and the synergistic effect of AA and CDRI-08 were studied in PC3 cell lines with and without growth factors. Nuclear staining with AO/EB and western blotting were performed to analyse apoptotic cell death and changes in protein expression of p-AKT and Casp3 in individual and combination-treated cells. RESULTS: CDRI-08 has shown no toxicity and teratogenicity in zebrafish embryos. AA and CDRI-08 have shown dose-dependent cytotoxic effects in PC3 cell lines with and without growth factors. Synergism was observed with different concentration ratios of AA and CDRI-08 with and without growth factors, with a good combination index (CI). Apoptosis was observed in individual and combination treated cells with an increase in Casp3 and simultaneous decrease in p-AKT expression levels. CONCLUSION: The study confirms the synergistic effect of CDRI-08 and AA at a lower dose, targeting the tyrosine kinase and androgen receptor pathways.