Moracin D induces apoptosis in prostate cancer cells via activation of PPAR gamma/PKC delta and inhibition of PKC alpha

Herein, apoptotic mechanism of Moracin D was explored in prostate cancer cells in association with peroxisome proliferator-activated receptor gamma (PPAR-gamma)-related signaling involved in lipid metabolism. Moracin D augmented cytotoxicity and sub G1 population in PC3 and DU145 prostate cancer cells, while DU145 cells were more susceptible to Moracin D than PC3 cells. Moracin D attenuated the expression of caspase-3, poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma-extra-large (Bcl-xL) in DU145 cells. Consistently, Moracin D significantly augmented the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in DU145 cells. Interestingly, Moracin D activated PPAR-gamma and phospho-protein kinase C delta (p-PKC-delta) and inhibited phospho-protein kinase C alpha (p-PKC-alpha) in DU145 cells. Furthermore, STRING bioinformatic analysis reveals that PPAR-gamma interacts with nuclear factor-kappa B (NF-kappa B) that binds to PKC-alpha/PKC-delta or protein kinase B (AKT) or extracellular signal-regulated kinase (ERK). Indeed, Moracin D decreased phosphorylation of NF-kappa B, ERK, and AKT in DU145 cells. Conversely, PPAR-gamma inhibitor GW9662 reduced the apoptotic ability of Moracin D to activate caspase 3 and PARP in DU145 cells. Taken together, these findings provide a novel insight that activation of PPAR-gamma/p-PKC-delta and inhibition of p-PKC-alpha are critically involved in Moracin D-induced apoptosis in DU145 prostate cancer cells.

Automated summary

Moracin D induces apoptosis in DU145 prostate cancer cells through activation of PPAR-gamma/p-PKC-delta signaling and inhibition of p-PKC-alpha. It downregulates caspase-3 and PARP expression, with DU145 cells showing higher sensitivity compared to PC3 cells. This highlights a novel mechanism by which Moracin D exerts its cytotoxic effects in prostate cancer.