1. Academic Validation
  2. Moracin D induces apoptosis in prostate cancer cells via activation of PPAR gamma/PKC delta and inhibition of PKC alpha

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

  • Phytother Res. 2021 Dec;35(12):6944-6953. doi: 10.1002/ptr.7313.
Jae Seok Yoon 1 Hyo-Jung Lee 1 Deok Yong Sim 1 Eunji Im 1 Ji Eon Park 1 Woon Yi Park 1 Ja Il Koo 1 Bum Sang Shim 1 Sung-Hoon Kim 1
Affiliations

Affiliation

  • 1 College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Abstract

Herein, apoptotic mechanism of Moracin D was explored in prostate Cancer cells in association with Peroxisome Proliferator-activated Receptor gamma (PPAR-γ)-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-γ and phospho-protein kinase C delta (p-PKC-δ) and inhibited phospho-protein kinase C alpha (p-PKC-α) in DU145 cells. Furthermore, STRING bioinformatic analysis reveals that PPAR-γ interacts with nuclear factor-κB (NF-κB) that binds to PKC-α/PKC-δ or protein kinase B (Akt) or extracellular signal-regulated kinase (ERK). Indeed, Moracin D decreased phosphorylation of NF-κB, ERK, and Akt in DU145 cells. Conversely, PPAR-γ 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-γ/p-PKC-δ and inhibition of p-PKC-α are critically involved in Moracin D-induced Apoptosis in DU145 prostate Cancer cells.

Keywords

Moracin D; PKC-α; PKC-δ; PPAR-γ; apoptosis; prostate cancer.

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