In:
Phytotherapy Research, Wiley, Vol. 35, No. 12 ( 2021-12), p. 6944-6953
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.
Type of Medium:
Online Resource
ISSN:
0951-418X
,
1099-1573
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1493490-5
SSG:
15,3
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