Synergistic Cytotoxic Effect of CDRI 08 in Combination with Abiraterone Targeting the EGFR PI3K AKT Pathway in Androgen Independent Prostate Cancer Cell Lines

Abstract

Prostate cancer is the second most commonly diagnosed cancer in men worldwide after lung cancer Androgen Deprivation Therapy has shown high risk of relapse to Castration Resistant Prostate Cancer and the development of drug resistance was found to reduce the survival rate Bacopa monnieri is a known ayurvedic medicinal plant and Central Drug Research Institute Lucknow has developed and patented a standardized fraction CDRI 08 which is in clinical use Combination therapy involves the use of multiple drugs to increase efficacy Therefore in the current study the combination effect of Abiraterone acetate and CDRI 08 was studied in PC3 cell lines targeting the interlinked Androgen Receptor and Epidermal growth factor receptor Phosphoinositide 3 kinase Protein kinase B signaling pathways newlineHigh Performance Thin Layer Chromatography and Gas Chromatography Mass Spectrometry analysis of CDRI 08 has shown the presence of Bacoside A and 24 compounds with various biological properties In vivo toxicity study of CDRI 08 in zebrafish embryos has not shown any toxicity and teratogenicity In silico molecular docking of the phytocomponents of CDRI 08 with the Epidermal Growth Factor Receptor Phosphoinositide 3 kinase Protein kinase and Extracellular Regulated Kinase have shown significant interactions with active site amino acids with good binding energy The in vitro cytotoxicity effect of Abiraterone acetate and CDRI 08 individually and in combination has shown good growth inhibitory effect with synergism and apoptosis induced cell death in PC3 cell lines CDRI 08 treated and combination treated groups in PC3 cell lines has shown upregulation in Casp3 expression and down regulation in phosphorylated protein kinase B expression Thus the study confirms potent anticancer activity of CDRI 08 individually and synergistically with abiraterone acetate on PC3 cell lines targeting the Epidermal growth factor receptor Phosphoinositide 3 kinase Protein kinase B pathway newline newline