In silicodocking of phytocompounds to identify potent inhibitors of signaling pathways involved in prostate cancer

Androgens and androgen receptors (AR) are the master regulators in the development of prostate cancer. Majority of the patients show positive response to surgical or medical castration, while many patients show disease relapse after the treatment. Genomic profiling has proven that the deregulated PI3K, Ras/Raf, MAPK and EGFR signaling pathways confer survival and invasion advantage to the cancer cells. Thus, modulation of these interlinked growth pathways along with androgen ablation may provide attractive therapeutic benefits. The current research is focused to identify the inhibitors of these pathways with bacosides and Piperine. The quantitative estimation of bacosides enriched standard extract ofBacopa monnieriby HPTLC showed 59.38% of Bacoside A and various active compounds with anti-oxidant, anti-cancer, anti-microbial, anti-inflammatory properties were also analyzed by GC-MS analysis. Thein-vitrocytotoxic study against PC3 cell lines showed dose-dependent effect of Piperine and the extract. Further,in silicodocking has shown bacosides with significant molecular interactions and binding score with growth factor receptors such as EGFR, PI3K, Akt and ERK, whereas Piperine exhibited interactions with AR. Hence, a simultaneous downregulation of interlinked signaling pathways of growth factors and AR with bacosides and Piperine may produce effective cytotoxic potential against the androgen-independent prostate cancer. Furtherin-vitroandin-vivoexperimental investigations are necessary to determine the ultimate therapeutic utility. Communicated by Ramaswamy H. Sarma